Skip to main content
SpringerLink
Log in

MicroRNAs regulating Wnt signaling pathway in colorectal cancer: biological implications and clinical potentials

  • Review
  • Published:
Functional & Integrative Genomics Aims and scope Submit manuscript

A Correction to this article was published on 23 November 2022

This article has been updated

Abstract

Colorectal cancer (CRC) is one of the most frequent cancers leading to death worldwide. Different signaling pathways such as the canonical Wnt signaling pathway have many effects on the development of CRC. MicroRNAs are small non-coding RNAs and different evidence represent their importance in the development of cancer via regulating the expression of their target genes. miRNAs can affect CRC progression as oncogenes or tumor suppressors. Dysregulation in miRNA expression can occur for various reasons, causes different abnormalities in the Wnt signaling pathway, and contributes to CRC development. Identifying the exact interactions between microRNAs and mRNAs or other non-coding RNAs assists in designing effective therapeutic, diagnostic, and prognostic approaches. In this review, we aim to focus on microRNAs that regulate CRC through modulating the Wnt pathway and then present the perspective outlook on the implication of miRNA in liquid biopsy for the management of patients with CRC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Not applicable.

Change history

References

  • Anfossi S, Babayan A, Pantel K, Calin GA (2018) Clinical utility of circulating non-coding RNAs - an update. Nat Rev Clin Oncol 15(9):541–563

    Article  PubMed  Google Scholar 

  • Ba S, Xuan Y, Long ZW, Chen HY, Zheng SS (2017) MicroRNA-27a promotes the proliferation and invasiveness of colon cancer cells by targeting SFRP1 through the Wnt/β-Catenin Signaling Pathway. Cell Physiol Biochem 42(5):1920–1933

    Article  PubMed  CAS  Google Scholar 

  • Baker NE (1987) Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos. EMBO J 6(6):1765–1773

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Basso K, Saito M, Sumazin P, Margolin AA, Wang K, Lim WK et al (2010) Integrated biochemical and computational approach identifies BCL6 direct target genes controlling multiple pathways in normal germinal center B cells. Blood 115(5):975–984

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bauer M, Bénard J, Gaasterland T, Willert K, Cappellen D (2013) WNT5A encodes two isoforms with distinct functions in cancers. PLoS ONE 8(11):e80526

    Article  PubMed  PubMed Central  Google Scholar 

  • Bollaert E, de Rocca SA, Demoulin J-B (2019) The HMG box transcription factor HBP1: a cell cycle inhibitor at the crossroads of cancer signaling pathways. Cell Mol Life Sci 76(8):1529–1539

    Article  PubMed  CAS  Google Scholar 

  • Brase JC, Wuttig D, Kuner R, Sültmann H (2010) Serum microRNAs as non-invasive biomarkers for cancer. Mol Cancer 9:306

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cao J, Yan XR, Liu T, Han XB, Yu JJ, Liu SH et al (2017) MicroRNA-552 promotes tumor cell proliferation and migration by directly targeting DACH1 via the Wnt/β-catenin signaling pathway in colorectal cancer. Oncol Lett 14(3):3795–3802

    Article  PubMed  PubMed Central  Google Scholar 

  • Cavallini A, Rotelli MT, Lippolis C, Piscitelli D, Digennaro R, Covelli C et al (2017) Human microRNA expression in sporadic and FAP-associated desmoid tumors and correlation with beta-catenin mutations. Oncotarget 8(26):41866–41875

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen Y, Song W (2018) Wnt/catenin β1/microRNA 183 predicts recurrence and prognosis of patients with colorectal cancer. Oncol Lett 15(4):4451–4456

    PubMed  PubMed Central  Google Scholar 

  • Chen TH, Chang SW, Huang CC, Wang KL, Yeh KT, Liu CN et al (2013) The prognostic significance of APC gene mutation and miR-21 expression in advanced-stage colorectal cancer. Colorectal Dis 15(11):1367–1374

    Article  PubMed  Google Scholar 

  • Chen B, Zhang D, Kuai J, Cheng M, Fang X, Li G (2017) Upregulation of miR-199a/b contributes to cisplatin resistance via Wnt/β-catenin-ABCG2 signaling pathway in ALDHA1(+) colorectal cancer stem cells. Tumour Biol 39(6):1010428317715155

    Article  PubMed  Google Scholar 

  • Chen HY, Lang YD, Lin HN, Liu YR, Liao CC, Nana AW et al (2019a) miR-103/107 prolong Wnt/β-catenin signaling and colorectal cancer stemness by targeting Axin2. Sci Rep 9(1):9687

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen B, Xia Z, Deng YN, Yang Y, Zhang P, Zhu H et al (2019b) Emerging microRNA biomarkers for colorectal cancer diagnosis and prognosis. Open Biol 9(1):180212

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen H, Pei L, Xie P, Guo G (2020) Circ-PRKDC Contributes to 5-fluorouracil resistance of colorectal cancer cells by regulating miR-375/FOXM1 axis and Wnt/β-catenin pathway. Onco Targets Ther 13:5939–5953

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cho WCS (2010) MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol 42(8):1273–1281

    Article  PubMed  CAS  Google Scholar 

  • Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D et al (2020) miRNAs as biomarkers in disease: latest findings regarding their role in diagnosis and prognosis. Cells 9(2):276

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cong J, Gong J, Yang C, Xia Z, Zhang H (2021) MiR-200c/FUT4 axis prevents the proliferation of colon cancer cells by downregulating the Wnt/β-catenin pathway. BMC Cancer 21(1):2-

  • Cui M, Wang H, Yao X, Zhang D, Xie Y, Cui R et al (2019) Circulating MicroRNAs in cancer: potential and challenge. Front Genet 10:626-

  • Dann CE, Hsieh JC, Rattner A, Sharma D, Nathans J, Leahy DJ (2001) Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains. Nature 412(6842):86–90

    Article  PubMed  CAS  Google Scholar 

  • Ding D, Li C, Zhao T, Li D, Yang L, Zhang B (2018) LncRNA H19/miR-29b-3p/PGRN axis promoted epithelial-mesenchymal transition of colorectal cancer cells by acting on Wnt signaling. Mol Cells 41(5):423–435

    PubMed  PubMed Central  CAS  Google Scholar 

  • Dokanehiifard S, Yasari A, Najafi H, Jafarzadeh M, Nikkhah M, Mowla SJ et al (2017) A novel microRNA located in the TrkC gene regulates the Wnt signaling pathway and is differentially expressed in colorectal cancer specimens. J Biol Chem 292(18):7566–7577

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dong-Xu W, Jia L, Su-Juan Z (2015) MicroRNA-185 is a novel tumor suppressor by negatively modulating the Wnt/β-catenin pathway in human colorectal cancer. Indian J Cancer 52(Suppl 3):E182–E185

    Article  PubMed  Google Scholar 

  • Dou H, Shen R, Tao J, Huang L, Shi H, Chen H et al (2017) Curcumin Suppresses the colon cancer proliferation by inhibiting Wnt/β-catenin pathways via miR-130a. Front Pharmacol 8:877

    Article  PubMed  PubMed Central  Google Scholar 

  • Du YL, Liang Y, Shi GQ, Cao Y, Qiu J, Yuan L et al (2020) LINC00689 participates in proliferation, chemoresistance and metastasis via miR-31-5p/YAP/β-catenin axis in colorectal cancer. Exp Cell Res 395(1):112176

    Article  PubMed  CAS  Google Scholar 

  • Duan W, Kong X, Li J, Li P, Zhao Y, Liu T et al (2020) LncRNA AC010789.1 promotes colorectal cancer progression by targeting MicroRNA-432–3p/ZEB1 axis and the Wnt/β-catenin signaling pathway. Front Cell Dev Biol. 8:565355

    Article  PubMed  PubMed Central  Google Scholar 

  • Duchartre Y, Kim Y-M, Kahn M (2016) The Wnt signaling pathway in cancer. Crit Rev Oncol Hematol 99:141–149

    Article  PubMed  Google Scholar 

  • Fang G, Ye BL, Hu BR, Ruan XJ, Shi YX (2018) CircRNA_100290 promotes colorectal cancer progression through miR-516b-induced downregulation of FZD4 expression and Wnt/β-catenin signaling. Biochem Biophys Res Commun 504(1):184–189

    Article  PubMed  CAS  Google Scholar 

  • Fasihi A, Soltani BM, Atashi A, Nasiri S (2018) Introduction of hsa-miR-103a and hsa-miR-1827 and hsa-miR-137 as new regulators of Wnt signaling pathway and their relation to colorectal carcinoma. J Cell Biochem 119(7):5104–17

    Article  PubMed  CAS  Google Scholar 

  • Fasihi A, Soltani BM, Ranjbaran ZS, Bahonar S, Norouzi R, Nasiri S (2019) Hsa-miR-942 fingerprint in colorectal cancer through Wnt signaling pathway. Gene 712:143958

    Article  PubMed  CAS  Google Scholar 

  • Feng ZY, Xu XH, Cen DZ, Luo CY, Wu SB (2017) miR-590-3p promotes colon cancer cell proliferation via Wnt/β-catenin signaling pathway by inhibiting WIF1 and DKK1. Eur Rev Med Pharmacol Sci 21(21):4844–4852

    PubMed  Google Scholar 

  • Ge X, Lv X, Feng L, Liu X, Gao J, Chen N et al (2012) Metadherin contributes to the pathogenesis of diffuse large B-cell lymphoma. PloS One 7(6):e39449-e

  • Gu C, Cai J, Xu Z, Zhou S, Ye L, Yan Q et al (2019) MiR-532-3p suppresses colorectal cancer progression by disrupting the ETS1/TGM2 axis-mediated Wnt/β-catenin signaling. Cell Death Dis 10(10):739

    Article  PubMed  PubMed Central  Google Scholar 

  • Guo YH, Wang LQ, Li B, Xu H, Yang JH, Zheng LS et al (2016) Wnt/β-catenin pathway transactivates microRNA-150 that promotes EMT of colorectal cancer cells by suppressing CREB signaling. Oncotarget 7(27):42513–42526

    Article  PubMed  PubMed Central  Google Scholar 

  • Guz M, Jeleniewicz W, Cybulski M (2022) An Insight into miR-1290: An Oncogenic miRNA with Diagnostic Potential. Int J Mol Sci 23(3):1234

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18(24):3016–3027

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Han P, Li JW, Zhang BM, Lv JC, Li YM, Gu XY et al (2017) The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling. Mol Cancer 16(1):9

    Article  PubMed  PubMed Central  Google Scholar 

  • Han X, Zheng J, Wang Y, Gao Z (2018) miRNA-29a inhibits colon cancer growth by regulation of the PTEN/Akt/GSK3β and Wnt/β-catenin signaling pathways. Oncol Lett 16(2):2638–2644

    PubMed  PubMed Central  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of Cancer: The Next Generation. Cell 144(5):646–674

    Article  PubMed  CAS  Google Scholar 

  • Hanson Alison J, Wallace Heather A, Freeman Tanner J, Beauchamp RD, Lee Laura A, Lee E (2012) XIAP Monoubiquitylates Groucho/TLE to Promote Canonical Wnt Signaling. Mol Cell 45(5):619–628

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • He Z, Dang J, Song A, Cui X, Ma Z, Zhang Y (2020) The involvement of miR-150/β-catenin axis in colorectal cancer progression. Biomed Pharmacother 121:109495

    Article  PubMed  CAS  Google Scholar 

  • Holloway KR, Calhoun TN, Saxena M, Metoyer CF, Kandler EF, Rivera CA et al (2010) SIRT1 regulates Dishevelled proteins and promotes transient and constitutive Wnt signaling. Proc Natl Acad Sci USA 107(20):9216–9221

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hongdan L, Feng L (2018) miR-3120-5p promotes colon cancer stem cell stemness and invasiveness through targeting Axin2. Biochem Biophys Res Commun 496(2):302–308

    Article  PubMed  Google Scholar 

  • Hou N, Huo D, Dignam JJ (2013) Prevention of colorectal cancer and dietary management. Chin Clin Oncol 2(2):13-

  • Hu X-X, Xu X-N, He B-S, Sun H-L, Xu T, Liu X-X et al (2018) microRNA-485-5p functions as a tumor suppressor in colorectal cancer cells by targeting CD147. J Cancer 9(15):2603–2611

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang L, Liu Z, Hu J, Luo Z, Zhang C, Wang L et al (2020) MiR-377-3p suppresses colorectal cancer through negative regulation on Wnt/β-catenin signaling by targeting XIAP and ZEB2. Pharmacol Res 156:104774

    Article  PubMed  CAS  Google Scholar 

  • Ji S, Ye G, Zhang J, Wang L, Wang T, Wang Z et al (2013) miR-574-5p negatively regulates Qki6/7 to impact β-catenin/Wnt signalling and the development of colorectal cancer. Gut 62(5):716–726

    Article  PubMed  CAS  Google Scholar 

  • Jia Y, Chen L, Guo S, Li Y (2019) Baicalin induced colon cancer cells apoptosis through miR-217/DKK1-mediated inhibition of Wnt signaling pathway. Mol Biol Rep 46(2):1693–1700

    Article  PubMed  CAS  Google Scholar 

  • Jiang S, Miao D, Wang M, Lv J, Wang Y, Tong J (2019) MiR-30-5p suppresses cell chemoresistance and stemness in colorectal cancer through USP22/Wnt/β-catenin signaling axis. J Cell Mol Med 23(1):630–640

    Article  PubMed  CAS  Google Scholar 

  • Jing N, Huang T, Guo H, Yang J, Li M, Chen Z et al (2018) LncRNA CASC15 promotes colon cancer cell proliferation and metastasis by regulating the miR-4310/LGR5/Wnt/β-catenin signaling pathway. Mol Med Rep 18(2):2269–2276

    PubMed  CAS  Google Scholar 

  • Kamatani A, Nakagawa Y, Akao Y, Maruyama N, Nagasaka M, Shibata T et al (2013) Downregulation of anti-oncomirs miR-143/145 cluster occurs before APC gene aberration in the development of colorectal tumors. Med Mol Morphol 46(3):166–171

    Article  PubMed  CAS  Google Scholar 

  • Kazanskaya O, Glinka A, del Barco BI, Stannek P, Niehrs C, Wu W (2004) R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis. Dev Cell 7(4):525–534

    Article  PubMed  CAS  Google Scholar 

  • Kim NH, Cha YH, Kang SE, Lee Y, Lee I, Cha SY et al (2013) p53 regulates nuclear GSK-3 levels through miR-34-mediated Axin2 suppression in colorectal cancer cells. Cell Cycle 12(10):1578–1587

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Komiya Y, Habas R (2008) Wnt signal transduction pathways. Organogenesis 4(2):68–75

    Article  PubMed  PubMed Central  Google Scholar 

  • Koveitypour Z, Panahi F, Vakilian M, Peymani M, Seyed Forootan F, Nasr Esfahani MH et al (2019) Signaling pathways involved in colorectal cancer progression. Cell Biosci 9:97-

  • Kwak B, Kim DU, Kim TO, Kim HS, Kim SW (2018) MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer. Int J Oncol 53(4):1800–1808

    PubMed  CAS  Google Scholar 

  • Lai PS, Chang WM, Chen YY, Lin Y, Liao HF, Chen CY (2021) Circulating microRNA-762 upregulates colorectal cancer may be accompanied by Wnt-1/β-catenin signaling. Cancer Biomark 32(2):111–122

  • Latres E, Chiaur DS, Pagano M (1999) The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin. Oncogene 18(4):849–854

    Article  PubMed  CAS  Google Scholar 

  • Li T, Lai Q, Wang S, Cai J, Xiao Z, Deng D et al (2016) MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer. J Exp Clin Cancer Res 35(1):21

    Article  PubMed  PubMed Central  Google Scholar 

  • Li T, Jian X, He H, Lai Q, Li X, Deng D et al (2018) MiR-452 promotes an aggressive colorectal cancer phenotype by regulating a Wnt/β-catenin positive feedback loop. J Exp Clin Cancer Res 37(1):238

    Article  PubMed  PubMed Central  Google Scholar 

  • Li S, Wu T, Zhang D, Sun X, Zhang X (2020a) The long non-coding RNA HCG18 promotes the growth and invasion of colorectal cancer cells through sponging miR-1271 and upregulating MTDH/Wnt/β-catenin. Clin Exp Pharmacol Physiol 47(4):703–712

    Article  PubMed  CAS  Google Scholar 

  • Li W, Xu Y, Wang X, Cao G, Bu W, Wang X et al (2020b) circCCT3 modulates vascular endothelial growth factor A and Wnt signaling to enhance colorectal cancer metastasis through sponging miR-613. DNA Cell Biol 39(1):118–125

    Article  PubMed  CAS  Google Scholar 

  • Liang J, Tang J, Shi H, Li H, Zhen T, Duan J et al (2017) miR-27a-3p targeting RXRα promotes colorectal cancer progression by activating Wnt/β-catenin pathway. Oncotarget 8(47):82991–83008

    Article  PubMed  PubMed Central  Google Scholar 

  • Lien WH, Fuchs E (2014) Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling. Genes Dev 28(14):1517–1532

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu X, Chen X, Zeng K, Xu M, He B, Pan Y et al (2018a) DNA-methylation-mediated silencing of miR-486-5p promotes colorectal cancer proliferation and migration through activation of PLAGL2/IGF2/β-catenin signal pathways. Cell Death Dis 9(10):1037

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu HN, Liu TT, Wu H, Chen YJ, Tseng YJ, Yao C et al (2018b) Serum microRNA signatures and metabolomics have high diagnostic value in colorectal cancer using two novel methods. Cancer Sci 109(4):1185–1194

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu D, Zhang H, Cui M, Chen C, Feng Y (2020) Hsa-miR-425-5p promotes tumor growth and metastasis by activating the CTNND1-mediated β-catenin pathway and EMT in colorectal cancer. Cell Cycle 19(15):1917–1927

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu Z, Gu Y, Cheng X, Jiang H, Huang Y, Zhang Y et al (2021a) Upregulation lnc-NEAT1 contributes to colorectal cancer progression through sponging miR-486-5p and activating NR4A1/Wnt/β-catenin pathway. Cancer Biomark 30(3):309–319

    Article  PubMed  CAS  Google Scholar 

  • Liu Q, Zhang W, Luo L, Han K, Liu R, Wei S et al (2021b) Long noncoding RNA TUG1 regulates the progression of colorectal cancer through miR-542-3p/TRIB2 axis and Wnt/β-catenin pathway. Diagn Pathol 16(1):47

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lu Y, Zhao X, Liu Q, Li C, Graves-Deal R, Cao Z et al (2017) lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling. Nat Med 23(11):1331–1341

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Luan XF, Wang L, Gai XF (2019) The miR-28–5p-CAMTA2 axis regulates colon cancer progression via Wnt/β-catenin signaling. J Cell Biochem

  • Lund E, Güttinger S, Calado A, Dahlberg JE, Kutay U (2004) Nuclear export of microRNA precursors. Science 303(5654):95–98

    Article  PubMed  CAS  Google Scholar 

  • Luo Y, Chen JJ, Lv Q, Qin J, Huang YZ, Yu MH et al (2019) Long non-coding RNA NEAT1 promotes colorectal cancer progression by competitively binding miR-34a with SIRT1 and enhancing the Wnt/β-catenin signaling pathway. Cancer Lett 440–441:11–22

    Article  PubMed  Google Scholar 

  • Luo J, Liu L, Shen J, Zhou N, Feng Y, Zhang N et al (2021) miR-576-5p promotes epithelial-to-mesenchymal transition in colorectal cancer by targeting the Wnt5a-mediated Wnt/β-catenin signaling pathway. Mol Med Rep 23(2):94

    Article  PubMed  CAS  Google Scholar 

  • Lv SY, Shan TD, Pan XT, Tian ZB, Liu XS, Liu FG et al (2018) The lncRNA ZEB1-AS1 sponges miR-181a-5p to promote colorectal cancer cell proliferation by regulating Wnt/β-catenin signaling. Cell Cycle 17(10):1245–1254

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lv S, Zhang J, He Y, Liu Q, Wang Z, Liu B et al (2020) MicroRNA-520e targets AEG-1 to suppress the proliferation and invasion of colorectal cancer cells through Wnt/GSK-3β/β-catenin signalling. Clin Exp Pharmacol Physiol 47(1):158–167

    Article  PubMed  CAS  Google Scholar 

  • MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17(1):9–26

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Metcalfe C, Mendoza-Topaz C, Mieszczanek J, Bienz M (2010) Stability elements in the LRP6 cytoplasmic tail confer efficient signalling upon DIX-dependent polymerization. J Cell Sci 123(Pt 9):1588–1599

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mishra J, Drummond J, Quazi SH, Karanki SS, Shaw JJ, Chen B et al (2013) Prospective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis. Crit Rev Oncol Hematol 86(3):232–250

    Article  PubMed  Google Scholar 

  • Mohammadi A, Mansoori B, Baradaran B (2016) The role of microRNAs in colorectal cancer. Biomed Pharmacother 84:705–713

    Article  PubMed  CAS  Google Scholar 

  • Moody L, He H, Pan YX, Chen H (2017) Methods and novel technology for microRNA quantification in colorectal cancer screening. Clin Epigenetics 9:119

    Article  PubMed  PubMed Central  Google Scholar 

  • Morgan RG, Mortensson E, Williams AC (2018) Targeting LGR5 in colorectal cancer: therapeutic gold or too plastic? Br J Cancer 118(11):1410–1418

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nadolny C, Dong X (2015) Liver receptor homolog-1 (LRH-1): a potential therapeutic target for cancer. Cancer Biol Ther 16(7):997–1004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nagel R, le Sage C, Diosdado B, van der Waal M, Oude Vrielink JA, Bolijn A et al (2008) Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer. Cancer Res 68(14):5795–5802

    Article  PubMed  CAS  Google Scholar 

  • Nedaeinia R, Sharifi M, Avan A, Kazemi M, Rafiee L, Ghayour-Mobarhan M et al (2016) Locked nucleic acid anti-miR-21 inhibits cell growth and invasive behaviors of a colorectal adenocarcinoma cell line: LNA-anti-miR as a novel approach. Cancer Gene Ther 23(8):246–253

    Article  PubMed  CAS  Google Scholar 

  • Niehrs C (2012) The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol 13(12):767–779

    Article  PubMed  CAS  Google Scholar 

  • Nusse R, van Ooyen A, Cox D, Fung YK, Varmus H (1984) Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature 307(5947):131–136

    Article  PubMed  CAS  Google Scholar 

  • Nusse R, Brown A, Papkoff J, Scambler P, Shackleford G, McMahon A et al (1991) A new nomenclature for int-1 and related genes: the Wnt gene family. Cell 64(2):231

    Article  PubMed  CAS  Google Scholar 

  • Nüsslein-Volhard C, Wieschaus E (1980) Mutations affecting segment number and polarity in Drosophila. Nature 287(5785):795–801

    Article  PubMed  Google Scholar 

  • Otmani K, Lewalle P (2021) Tumor suppressor miRNA in cancer cells and the tumor microenvironment: mechanism of deregulation and clinical implications. Front Oncol 11

  • Pan S, Wu W, Ren F, Li L, Li Y, Li W et al (2020) MiR-346-5p promotes colorectal cancer cell proliferation in vitro and in vivo by targeting FBXL2 and activating the β-catenin signaling pathway. Life Sci 244:117300

    Article  PubMed  CAS  Google Scholar 

  • Peng Y, Croce CM (2016) The role of MicroRNAs in human cancer. Signal Transduct Target Ther 1(1):15004

    Article  PubMed  PubMed Central  Google Scholar 

  • Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC (2000) An LDL-receptor-related protein mediates Wnt signalling in mice. Nature 407(6803):535–538

    Article  PubMed  CAS  Google Scholar 

  • Qu R, Hao S, Jin X, Shi G, Yu Q, Tong X et al (2018) MicroRNA-374b reduces the proliferation and invasion of colon cancer cells by regulation of LRH-1/Wnt signaling. Gene 642:354–361

    Article  PubMed  CAS  Google Scholar 

  • Rennoll S, Yochum G (2015) Regulation of MYC gene expression by aberrant Wnt/β-catenin signaling in colorectal cancer. World J Biol Chem 6(4):290–300

    Article  PubMed  PubMed Central  Google Scholar 

  • Saberinia A, Alinezhad A, Jafari F, Soltany S, Akhavan SR (2020) Oncogenic miRNAs and target therapies in colorectal cancer. Clin Chim Acta 508:77–91

    Article  PubMed  CAS  Google Scholar 

  • Saieva L, Barreca MM, Zichittella C, Prado MG, Tripodi M, Alessandro R et al (2020) Hypoxia-induced miR-675–5p supports β-catenin nuclear localization by regulating GSK3-β activity in colorectal cancer cell lines. Int J Mol Sci 21(11)

  • Schatoff EM, Leach BI, Dow LE (2017) Wnt signaling and colorectal cancer. Curr Colorectal Cancer Rep 13(2):101–110

    Article  PubMed  PubMed Central  Google Scholar 

  • Semënov M, Tamai K, He X (2005) SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 280(29):26770–26775

    Article  PubMed  Google Scholar 

  • Shao Q, Xu J, Deng R, Wei W, Zhou B, Yue C et al (2019) SNHG 6 promotes the progression of colon and rectal adenocarcinoma via miR-101-3p and Wnt/β-catenin signaling pathway. BMC Gastroenterol 19(1):163

    Article  PubMed  PubMed Central  Google Scholar 

  • Sharifi M, Salehi R, Gheisari Y, Kazemi M (2014) Inhibition of microRNA miR-92a induces apoptosis and inhibits cell proliferation in human acute promyelocytic leukemia through modulation of p63 expression. Mol Biol Rep 41(5):2799–2808

    Article  PubMed  CAS  Google Scholar 

  • Shenoy AK, Fisher RC, Butterworth EA, Pi L, Chang LJ, Appelman HD et al (2012) Transition from colitis to cancer: high Wnt activity sustains the tumor-initiating potential of colon cancer stem cell precursors. Cancer Res 72(19):5091–5100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shi L, Xi J, Xu X, Peng B, Zhang B (2019) MiR-148a suppressed cell invasion and migration via targeting WNT10b and modulating β-catenin signaling in cisplatin-resistant colorectal cancer cells. Biomed Pharmacother 109:902–909

    Article  PubMed  CAS  Google Scholar 

  • Shu Z, Chen L, Ding D (2016) miR-582-5P induces colorectal cancer cell proliferation by targeting adenomatous polyposis coli. World J Surg Oncol 14(1):239

    Article  PubMed  PubMed Central  Google Scholar 

  • Shukla GC, Singh J, Barik S (2011) MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol 3(3):83–92

    PubMed  PubMed Central  CAS  Google Scholar 

  • Si W, Shen J, Zheng H, Fan W (2019) The role and mechanisms of action of microRNAs in cancer drug resistance. Clin Epigenetics 11(1):25

    Article  PubMed  PubMed Central  Google Scholar 

  • Siemens H, Neumann J, Jackstadt R, Mansmann U, Horst D, Kirchner T et al (2013) Detection of miR-34a promoter methylation in combination with elevated expression of c-Met and β-catenin predicts distant metastasis of colon cancer. Clin Cancer Res 19(3):710–720

    Article  PubMed  CAS  Google Scholar 

  • Subramanian M, Rao SR, Thacker P, Chatterjee S, Karunagaran D (2014) MiR-29b downregulates canonical Wnt signaling by suppressing coactivators of β-catenin in human colorectal cancer cells. J Cell Biochem 115(11):1974–1984

    PubMed  CAS  Google Scholar 

  • Sun JY, Huang Y, Li JP, Zhang X, Wang L, Meng YL et al (2012) MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting β-catenin. Biochem Biophys Res Commun 420(4):787–792

    Article  PubMed  CAS  Google Scholar 

  • Sun N, Zhang G, Liu Y (2018) Long non-coding RNA XIST sponges miR-34a to promotes colon cancer progression via Wnt/β-catenin signaling pathway. Gene 665:141–148

    Article  PubMed  CAS  Google Scholar 

  • Sun R, Liu Z, Han L, Yang Y, Wu F, Jiang Q et al (2019) miR-22 and miR-214 targeting BCL9L inhibit proliferation, metastasis, and epithelial-mesenchymal transition by down-regulating Wnt signaling in colon cancer. Faseb j 33(4):5411–5424

    Article  PubMed  CAS  Google Scholar 

  • Sun N, Zhang L, Zhang C, Yuan Y (2020) miR-144-3p inhibits cell proliferation of colorectal cancer cells by targeting BCL6 via inhibition of Wnt/β-catenin signaling. Cell Mol Biol Lett 25:19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sun X, Zhai H, Chen X, Kong R, Zhang X (2018) MicroRNA-1271 suppresses the proliferation and invasion of colorectal cancer cells by regulating metadherin/Wnt signaling. J Biochem Mol Toxicol 32(2)

  • Tang Q, Zou Z, Zou C, Zhang Q, Huang R, Guan X et al (2015) MicroRNA-93 suppress colorectal cancer development via Wnt/β-catenin pathway downregulating. Tumour Biol 36(3):1701–1710

    Article  PubMed  CAS  Google Scholar 

  • Thanikachalam K, Khan G (2019) Colorectal cancer and nutrition. Nutrients 11(1):164

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tiberio P, Callari M, Angeloni V, Daidone MG, Appierto V (2015) Challenges in Using Circulating miRNAs as Cancer Biomarkers. Biomed Res Int 2015:731479

    Article  PubMed  PubMed Central  Google Scholar 

  • Wan YC, Li T, Han YD, Zhang HY, Lin H, Zhang B (2016) MicroRNA-155 enhances the activation of Wnt/β-catenin signaling in colorectal carcinoma by suppressing HMG-box transcription factor 1. Mol Med Rep 13(3):2221–2228

    Article  PubMed  CAS  Google Scholar 

  • Wang W, Xiao X, Chen X, Huo Y, Xi WJ, Lin ZF et al (2018) Tumor-suppressive miR-145 co-repressed by TCF4-β-catenin and PRC2 complexes forms double-negative regulation loops with its negative regulators in colorectal cancer. Int J Cancer 142(2):308–321

    Article  PubMed  CAS  Google Scholar 

  • Wang G, Zhou J, Lu F, Qiu L, Xu L, Yang X et al (2019a) Downregulation of microRNA-183-5p inhibits the proliferation and invasion of colorectal cancer cells by inactivating the reticulocalbin-2/Wnt/β-catenin signaling pathway. Mol Med Rep 19(5):4475–4483

    PubMed  CAS  Google Scholar 

  • Wang W, He Y, Rui J, Xu MQ (2019b) miR-410 acts as an oncogene in colorectal cancer cells by targeting dickkopf-related protein 1 via the Wnt/β-catenin signaling pathway. Oncol Lett 17(1):807–814

    PubMed  CAS  Google Scholar 

  • Wu F, Xing T, Gao X, Liu F (2019) miR-501-3p promotes colorectal cancer progression via activation of Wnt/β-catenin signaling. Int J Oncol 55(3):671–683

    PubMed  PubMed Central  Google Scholar 

  • Wu SY, Huang YJ, Tzeng YM, Huang CF, Hsiao M, Wu ATH et al (2018) Destruxin B suppresses drug-resistant colon tumorigenesis and stemness is associated with the upregulation of miR-214 and downregulation of mTOR/β-catenin pathway. Cancers (Basel) 10(10)

  • Wu J, Chen Z, Liu W, Zhang Y, Feng W, Yuan Y et al (2020) MicroRNA-188–5p targeting Forkhead Box L1 promotes colorectal cancer progression via activating Wnt/β-catenin signaling. Oncol Res

  • Xiao Z, Qu Z, Chen Z, Fang Z, Zhou K, Huang Z et al (2018) LncRNA HOTAIR is a prognostic biomarker for the proliferation and chemoresistance of colorectal cancer via MiR-203a-3p-mediated Wnt/ß-catenin signaling pathway. Cell Physiol Biochem 46(3):1275–1285

    Article  PubMed  CAS  Google Scholar 

  • Xiao F, Chen W, Yu C, Zhao G (2020) MicroRNA-663b enhances migration and invasion by targeting adenomatous polyposis coli 2 in colorectal carcinoma cells. Oncol Lett 19(6):3701–3710

    PubMed  PubMed Central  CAS  Google Scholar 

  • Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C et al (2004) Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116(6):883–895

    Article  PubMed  CAS  Google Scholar 

  • Yadav VK, Huang YJ, George TA, Wei PL, Sumitra MR, Ho CL et al (2020) Preclinical Evaluation of the Novel Small-Molecule MSI-N1014 for Treating Drug-Resistant Colon Cancer via the LGR5/β-catenin/miR-142–3p Network and Reducing Cancer-Associated Fibroblast Transformation. Cancers 12(6)

  • Yamada N, Noguchi S, Mori T, Naoe T, Maruo K, Akao Y (2013) Tumor-suppressive microRNA-145 targets catenin δ-1 to regulate Wnt/β-catenin signaling in human colon cancer cells. Cancer Lett 335(2):332–342

    Article  PubMed  CAS  Google Scholar 

  • Yan W, Wu K, Herman JG, Brock MV, Fuks F, Yang L et al (2013) Epigenetic regulation of DACH1, a novel Wnt signaling component in colorectal cancer. Epigenetics 8(12):1373–1383

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang W, Ning N, Jin X (2017) The lncRNA H19 Promotes Cell Proliferation by Competitively Binding to miR-200a and Derepressing β-Catenin Expression in Colorectal Cancer. Biomed Res Int 2017:2767484

    PubMed  PubMed Central  Google Scholar 

  • Yang K, Jiang B, Lu Y, Shu Q, Zhai P, Zhi Q et al (2019) FOXM1 promotes the growth and metastasis of colorectal cancer via activation of β-catenin signaling pathway. Cancer Manag Res 11:3779–3790

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang L, Bi T, Zhou S, Lan Y, Zhang R (2021) CircRASSF2 facilitates the proliferation and metastasis of colorectal cancer by mediating the activity of Wnt/β-catenin signaling pathway by regulating the miR-195–5p/FZD4 axis. Anti-Cancer Drugs

  • Ye K, Xu C, Hui T (2019) MiR-34b inhibits the proliferation and promotes apoptosis in colon cancer cells by targeting Wnt/β-catenin signaling pathway. Biosci Rep 39(10)

  • Yu B, Ye X, Du Q, Zhu B, Zhai Q, Li XX (2017) The long non-coding RNA CRNDE promotes colorectal carcinoma progression by competitively binding miR-217 with TCF7L2 and enhancing the Wnt/β-catenin signaling pathway. Cell Physiol Biochem 41(6):2489–2502

    Article  PubMed  CAS  Google Scholar 

  • Yu FB, Sheng J, Yu JM, Liu JH, Qin XX, Mou B (2020a) MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells. World J Gastroenterol 26(6):627–644

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yu Y, Chang Z, Han C, Zhuang L, Zhou C, Qi X et al (2020b) Long non-coding RNA MINCR aggravates colon cancer via regulating miR-708-5p-mediated Wnt/β-catenin pathway. Biomed Pharmacother 129:110292

    Article  PubMed  CAS  Google Scholar 

  • Yuan Q, Cao G, Li J, Zhang Y, Yang W (2017) MicroRNA-136 inhibits colon cancer cell proliferation and invasion through targeting liver receptor homolog-1/Wnt signaling. Gene 628:48–55

    Article  PubMed  CAS  Google Scholar 

  • Zhan T, Rindtorff N, Boutros M (2017) Wnt signaling in cancer. Oncogene 36(11):1461–1473

    Article  PubMed  CAS  Google Scholar 

  • Zhang JX, Mai SJ, Huang XX, Wang FW, Liao YJ, Lin MC et al (2014) MiR-29c mediates epithelial-to-mesenchymal transition in human colorectal carcinoma metastasis via PTP4A and GNA13 regulation of β-catenin signaling. Ann Oncol 25(11):2196–2204

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Xu J, Jiang T, Liu G, Wang D, Lu Y (2016) MicroRNA-195 suppresses colorectal cancer cells proliferation via targeting FGF2 and regulating Wnt/β-catenin pathway. Am J Cancer Res 6(11):2631–2640

    PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang GJ, Li LF, Yang GD, Xia SS, Wang R, Leng ZW et al (2017) MiR-92a promotes stem cell-like properties by activating Wnt/β-catenin signaling in colorectal cancer. Oncotarget 8(60):101760–101770

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Guo L, Li Y, Feng GH, Teng F, Li W et al (2018a) MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer. Mol Cancer 17(1):1

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Tian S, Xiong J, Zhou Y, Song H, Liu C (2018b) JQ-1 inhibits colon cancer proliferation via suppressing Wnt/β-catenin signaling and miR-21. Chem Res Toxicol 31(5):302–307

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Sun M, Chen Y, Li B (2019) MiR-519b-3p Inhibits the proliferation and invasion in colorectal cancer via modulating the uMtCK/Wnt signaling pathway. Front Pharmacol 10:741

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Y, Meng H, Guo K (2020) Inhibition of MicroRNA-302c on stemness of colon cancer stem cells via the CARF/Wnt/β-catenin axis. Dig Dis Sci

  • Zhang G, Liu Z, Zhong J, Lin L (2021) Circ-ACAP2 facilitates the progression of colorectal cancer through mediating miR-143–3p/FZD4 axis. Eur J Clin Investig e13607

  • Zheng K, Zhou X, Yu J, Li Q, Wang H, Li M et al (2016) Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/β-catenin signaling pathway. Cancer Lett 376(1):178–187

    Article  PubMed  CAS  Google Scholar 

  • Zheng Q, Yu JJ, Li C, Li J, Wang J, Wang S (2020) miR-224 targets BTRC and promotes cell migration and invasion in colorectal cancer. 3 Biotech 10(11):485-

  • Zhou C, Cui F, Li J, Wang D, Wei Y, Wu Y et al (2017) MiR-650 represses high-risk non-metastatic colorectal cancer progression via inhibition of AKT2/GSK3β/E-cadherin pathway. Oncotarget 8(30):49534–49547

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou T, Wu L, Ma N, Tang F, Zong Z, Chen S (2020) LncRNA PART1 regulates colorectal cancer via targeting miR-150-5p/miR-520h/CTNNB1 and activating Wnt/β-catenin pathway. Int J Biochem Cell Biol 118:105637

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

This work was supported by Isfahan University of Medical Sciences (Grant NO: 398985).

Author information

Authors and Affiliations

  1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Faeze Ahmadi Beni, Mohammad Kazemi & Hassan Dianat-Moghadam

  2. Reproductive Sciences and Sexual Health Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohammad Kazemi

  3. Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

    Mohadeseh Behjati

Authors
  1. Faeze Ahmadi Beni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Kazemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hassan Dianat-Moghadam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohadeseh Behjati
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Collected the data and wrote the article: F. A.; revised and supervised the article: H. D-M. and M. K; Edited the article: M.B and H.D-M.

Corresponding author

Correspondence to Mohammad Kazemi.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Human and animal ethics

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised: The above article was published with error. Figures 1 and 2 has been interchanged. This has been updated now.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Beni, F.A., Kazemi, M., Dianat-Moghadam, H. et al. MicroRNAs regulating Wnt signaling pathway in colorectal cancer: biological implications and clinical potentials. Funct Integr Genomics 22, 1073–1088 (2022). https://doi.org/10.1007/s10142-022-00908-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10142-022-00908-x

Keywords

Search

Navigation