Abstract
Objective
Colorectal cancer is one of the most common gastrointestinal tumors. The role of Wnt7b as a ligand of the Wnt signaling pathway in colorectal cancer remains to be studied. Through bioinformatics online analysis, we found that Wnt7b is abnormally highly expressed in a variety of gastrointestinal tumors. This study mainly explored the effects of Wnt7b regulating the Wnt/β-catenin signaling pathway on the proliferation, migration, and invasion of SW480 cells in colorectal cancer.
Methods and results
Applying the TCGA data set, Wnt7b was found to be highly expressed in most gastrointestinal tumor samples. Real-time quantitative PCR(q-PCR), Western blotting(WB) results showed that Wnt7b was significantly higher expressed in colorectal cancer cell lines compared with normal intestinal epithelial cells. SW480 cells transfected with the sh-Wnt7b showed successful knockdown of Wnt7b. MTT colorimetry showed the proliferation ability of sh-Wnt7b group decreased significantly compared with the non-transfected group. The results of double staining flow cytometry showed that the sh-Wnt7b group had more apoptosis. Cell scratch test showed that the cell migration rate of sh-wnt7b group considerably reduced. The Transwell invasion experiment demonstrated that the number of cell invasions in the sh-Wnt7b group decreased significantly. After SW480 cells was transfected with sh-Wnt7b, the protein levels of β-catenin, CCND1, and CD44 in this group of cells were detected to be reduced by WB, and the same results were obtained by q-PCR detection of mRNA.
Conclusion
Wnt7b is highly expressed in colorectal cancer cells, which may affect the proliferation, migration, and invasion of colorectal cancer cells by activating the Wnt/β-catenin signaling pathway.
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References
Hull R, Francies FZ, Oyomno M, Dlamini Z (2020) Colorectal Cancer Genetics, incidence and risk factors: in search for targeted therapies. Cancer Manage Res 12:9869–9882
Liu P, Cao F, Sui J, Hong Y, Liu Q, Gao X, Gong H, Hao L, Lou Z, Zhang W (2020) MicroRNA-142-3p inhibits tumorigenesis of Colorectal Cancer via suppressing the activation of wnt signaling by directly targeting to β-Catenin. Front Oncol 10:552944
Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, Jemal A, Kramer JL, Siegel RL (2019) Cancer treatment and survivorship statistics, 2019. Cancer J Clin 69(5):363–385
Zhong Z, Virshup DM (2020) Wnt signaling and Drug Resistance in Cancer. Mol Pharmacol 97(2):72–89
Taciak B, Pruszynska I, Kiraga L, Bialasek M, Krol M (2018) : Wnt signaling pathway in development and cancer.Journal of physiology and pharmacology: an official journal of the Polish Physiological Society69(2)
Nusse R, Clevers H (2017) Wnt/β-Catenin signaling, Disease, and emerging therapeutic modalities. Cell 169(6):985–999
Krishnamurthy N, Kurzrock R (2018) Targeting the Wnt/beta-catenin pathway in cancer: update on effectors and inhibitors. Cancer Treat Rev 62:50–60
Alamoud KA, Kukuruzinska MA (2018) Emerging insights into Wnt/β-catenin signaling in Head and Neck Cancer. J Dent Res 97(6):665–673
Lybrand DB, Naiman M, Laumann JM, Boardman M, Petshow S, Hansen K, Scott G, Wehrli M (2019) : Destruction complex dynamics: Wnt/β-catenin signaling alters Axin-GSK3β interactions in vivo. Development (Cambridge, England) 146(13)
Haseeb M, Pirzada RH, Ain QU, Choi S (2019) : Wnt signaling in the regulation of Immune Cell and Cancer therapeutics.Cells8(11)
Russell JO, Monga SP (2018) Wnt/β-Catenin signaling in Liver Development, Homeostasis, and Pathobiology. Annu Rev Pathol 13:351–378
Lee SK, Hwang JH, Choi KY (2018) Interaction of the Wnt/β-catenin and RAS-ERK pathways involving co-stabilization of both β-catenin and RAS plays important roles in the colorectal tumorigenesis. Adv Biol Regul 68:46–54
Cheng X, Xu X, Chen D, Zhao F, Wang W (2019) Therapeutic potential of targeting the Wnt/β-catenin signaling pathway in colorectal cancer. Biomed pharmacotherapy = Biomedecine pharmacotherapie 110:473–481
Ni Y, Lu C, Wang W, Gao W, Yu C (2021) circBANP promotes colorectal cancer growth and metastasis via sponging let-7d-5p to modulate HMGA1/Wnt/β-catenin signaling. Mol therapy oncolytics 21:119–133
Yamamoto H, Sakane H, Yamamoto H, Michiue T, Kikuchi A (2008) Wnt3a and Dkk1 regulate distinct internalization pathways of LRP6 to tune the activation of beta-catenin signaling. Dev Cell 15(1):37–48
Cho C, Smallwood PM, Nathans J (2017) Reck and Gpr124 are essential receptor cofactors for Wnt7a/Wnt7b-Specific signaling in mammalian CNS angiogenesis and blood-brain barrier regulation. Neuron 95(5):1221–1225
Gao Q, Yang L, Shen A, Li Y, Li Y, Hu S, Yang R, Wang X, Yao X, Shen G (2021) A WNT7B-m(6)A-TCF7L2 positive feedback loop promotes gastric cancer progression and metastasis. Signal Transduct Target therapy 6(1):43
Ali I, Medegan B, Braun DP (2016) Wnt9A induction linked to suppression of human colorectal Cancer cell proliferation. Int J Mol Sci 17(4):495
Yu F, Fan X, Chen B, Dong P, Zheng J (2016) Activation of hepatic stellate cells is inhibited by microRNA-378a-3p via Wnt10a. Cell Physiol biochemistry: Int J experimental Cell Physiol Biochem Pharmacol 39(6):2409–2420
Cui H, Zhao J (2020) LncRNA TMPO-AS1 serves as a ceRNA to promote osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis. J Cell Biochem 121(3):2284–2293
Qiu JJ, Sun SG, Tang XY, Lin YY, Hua KQ (2020) Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the β-catenin signaling pathway. J experimental Clin cancer research: CR 39(1):260
Tang N, Cai X, Peng L, Liu H, Chen Y (2020) TCP1 regulates Wnt7b/β-catenin pathway through P53 to influence the proliferation and migration of hepatocellular carcinoma cells. Signal Transduct Target therapy 5(1):169
Ruan GT, Zhu LC, Gong YZ, Liao XW, Wang XK, Liao C, Wang S, Yan L, Xie HL, Zhou X et al (2020) The diagnosis and prognosis values of WNT mRNA expression in colon adenocarcinoma. J Cell Biochem 121(5–6):3145–3161
Chen J, Liu TY, Peng HT, Wu YQ, Zhang LL, Lin XH, Lai YH (2018) Up-regulation of Wnt7b rather than Wnt1, Wnt7a, and Wnt9a indicates poor prognosis in breast cancer. Int J Clin Exp Pathol 11(9):4552–4561
Routledge D, Scholpp S (2019) : Mechanisms of intercellular wnt transport.Development (Cambridge, England)146(10)
Nie X, Liu H, Liu L, Wang YD, Chen WD (2020) Emerging roles of wnt ligands in human colorectal Cancer. Front Oncol 10:1341
Bian J, Dannappel M, Wan C, Firestein R (2020) : Transcriptional regulation of Wnt/β-Catenin pathway in Colorectal Cancer.Cells9(9)
Aizawa T, Karasawa H, Funayama R, Shirota M, Suzuki T, Maeda S, Suzuki H, Yamamura A, Naitoh T, Nakayama K et al (2019) Cancer-associated fibroblasts secrete Wnt2 to promote cancer progression in colorectal cancer. Cancer Med 8(14):6370–6382
Huang TC, Lee PT, Wu MH, Huang CC, Ko CY, Lee YC, Lin DY, Cheng YW, Lee KH (2017) Distinct roles and differential expression levels of Wnt5a mRNA isoforms in colorectal cancer cells. PLoS ONE 12(8):e0181034
Qi L, Sun B, Liu Z, Cheng R, Li Y, Zhao X (2014) Wnt3a expression is associated with epithelial-mesenchymal transition and promotes colon cancer progression. J experimental Clin cancer research: CR 33(1):107
Li J, Zhang Z, Wang L, Zhang Y (2019) The oncogenic role of Wnt10a in colorectal cancer through activation of canonical Wnt/β-catenin signaling. Oncol Lett 17(4):3657–3664
Qu Y, Olsen JR, Yuan X, Cheng PF, Levesque MP, Brokstad KA, Hoffman PS, Oyan AM, Zhang W, Kalland KH et al (2018) Small molecule promotes β-catenin citrullination and inhibits wnt signaling in cancer. Nat Chem Biol 14(1):94–101
Ding X, Du J, Mao K, Wang X, Ding Y, Wang F (2019) MicroRNA-143-3p suppresses tumorigenesis by targeting catenin-δ1 in colorectal cancer. OncoTargets and therapy 12:3255–3265
Yang JF, Shi SN, Xu WH, Qiu YH, Zheng JZ, Yu K, Song XY, Li F, Wang Y, Wang R et al (2019) Screening, identification and validation of CCND1 and PECAM1/CD31 for predicting prognosis in renal cell carcinoma patients. Aging 11(24):12057–12079
Yan F, Ma Y, Liu L, Li L, Deng J, Sun J (2020) Long noncoding RNA HOXD-AS1 promotes the Proliferation, Migration, and Invasion of Colorectal Cancer via the miR-526b-3p/CCND1 Axis. J Surg Res 255:525–535
Yan X, Han D, Chen Z, Han C, Dong W, Han L, Zou L, Zhang J, Liu Y, Chai J (2020) RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells. Cancer Cell Int 20:505
Mohamed SY, Kaf RM, Ahmed MM, Elwan A, Ashour HR, Ibrahim A (2019) The Prognostic Value of Cancer Stem cell markers (Notch1, ALDH1, and CD44) in primary colorectal carcinoma. J Gastrointest cancer 50(4):824–837
Gavin BJ, McMahon AP (1992) Differential regulation of the wnt gene family during pregnancy and lactation suggests a role in postnatal development of the mammary gland. Mol Cell Biol 12(5):2418–2423
Zhang Z, Xu Y, Zhao C (2021) Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer. Cancer Med 10(10):3332–3345
Sundqvist A, Morikawa M, Ren J, Vasilaki E, Kawasaki N, Kobayashi M, Koinuma D, Aburatani H, Miyazono K, Heldin CH et al (2018) JUNB governs a feed-forward network of TGFβ signaling that aggravates breast cancer invasion. Nucleic Acids Res 46(3):1180–1195
Yeo EJ, Cassetta L, Qian BZ, Lewkowich I, Li JF, Stefater JA 3, Smith AN, Wiechmann LS, Wang Y, Pollard JW et al (2014) Myeloid WNT7b mediates the angiogenic switch and metastasis in breast cancer. Cancer Res 74(11):2962–2973
Jiang S, Li Q, Liu Y, Zhang H, Wang Q, Chen Y, Shi X, Li J, Zhang H, Zhang Y et al (2021) Activation of WNT7b autocrine eases metastasis of colorectal cancer via epithelial to mesenchymal transition and predicts poor prognosis. BMC Cancer 21(1):180
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This study was funded by National Natural Science Foundation of China. (Grant number 31671092).
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Siyang Chen, Hui Ding and Kaiyun Wang contributed equally and shared the first authorship. All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Hui Ding and Kaiyun Wang. The first draft of the manuscript was written by Siyang Chen. All authors read and approved the final manuscript.
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Chen, S., Ding, H., Wang, K. et al. Inhibition of Wnt7b reduces the proliferation, invasion, and migration of colorectal cancer cells. Mol Biol Rep 50, 1415–1424 (2023). https://doi.org/10.1007/s11033-022-08106-5
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DOI: https://doi.org/10.1007/s11033-022-08106-5