Skip to main content

Advertisement

Log in

microRNA-4429-5p suppresses the malignant development of colon cancer by targeting matrix metalloproteinase 16

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Colon cancer has been recognized as the major reason for global cancer-associated mortality. microRNA (miRNA, miR)-4429-5p has been documented to act as a tumor-suppressive miRNA in some cancers, but its effect on colon cancer remains elusive. In this study, the biological effects of miR-4429-5p were investigated both in vitro by MTT, 5-ethynyl-2′-deoxyuridine (EdU), wound healing, and transwell assays and in vivo by a xenograft mice model. Western blot, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and dual-luciferase assay were used to identify the binding of miR-4429-5p on matrix metalloproteinase 16 (MMP16) 3′-UTR. Our results suggested that overexpression of miR-4429-5p hindered colon cancer cell proliferation, migration, and invasion, whereas knockdown of miR-4429-5p exhibited the opposite effect in colon cancer cells. Mechanistically, miR-4429-5p directly bound to the 3′-UTR of MMP16 and led to inhibition of MMP16 protein. Overexpression of miR-4429-5p inhibited colon tumor growth by targeting MMP16. Taken together, our study revealed that miR-4429-5p prevented colon cancer progression through targeting MMP16, indicating miR-4429-5p as a promising target for treatment improvement for colon cancer.

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

Access this article

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

Instant access to the full article PDF.

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  • Brenner H, Kloor M, Pox CP (2014) Colorectal cancer. Lancet 383(9927):1490–1502

    Article  Google Scholar 

  • Cao L, Chen C, Zhu H, Gu X, Deng D, Tian X, Liu J, Xiao Q (2016) MMP16 is a marker of poor prognosis in gastric cancer promoting proliferation and invasion. Oncotarget 7(32):51865–51874

    Article  Google Scholar 

  • Esquela-Kerscher A, Slack FJ (2006) Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269

    Article  CAS  Google Scholar 

  • Gungormez C, Gumushan Aktas H, Dilsiz N, Borazan E (2019) Novel miRNAs as potential biomarkers in stage II colon cancer: microarray analysis. Mol Biol Rep 46(4):4175–4183

    Article  CAS  Google Scholar 

  • He H, Wu W, Sun Z, Chai L (2019) MiR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m(6)A-caused stabilization of SEC62. Biochem Biophys Res Commun 517(4):581–587

    Article  CAS  Google Scholar 

  • Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10(2):126–139

    Article  CAS  Google Scholar 

  • Li Y, Wang Y, Yu L, Sun C, Cheng D, Yu S, Wang Q, Yan Y, Kang C, Jin S, An T, Shi C, Xu J, Wei C, Liu J, Sun J, Wen Y, Zhao S, Kong Y (2013) miR-146b-5p inhibits glioma migration and invasion by targeting MMP16. Cancer Lett 339(2):260–269

    Article  CAS  Google Scholar 

  • Liang L, Zheng YW, Wang YL (2020) miR-4429 Regulates the proliferation, migration, invasion, and epithelial-mesenchymal transition of cervical cancer by targeting FOXM1. Cancer Manag Res 12:5301–5312

    Article  CAS  Google Scholar 

  • Lin S, Gregory RI (2015) MicroRNA biogenesis pathways in cancer. Nat Rev Cancer 15(6):321–333

    Article  CAS  Google Scholar 

  • Liu X, Chen R, Liu L (2019) SP1-DLEU1-miR-4429 feedback loop promotes cell proliferative and anti-apoptotic abilities in human glioblastoma. Biosci Rep 39(12)

  • Liu Y, Chen X, Cheng R, Yang F, Yu M, Wang C, Cui S, Hong Y, Liang H, Liu M, Zhao C, Ding M, Sun W, Liu Z, Sun F, Zhang C, Zhou Z, Jiang X, Chen X (2018) The Jun/miR-22/HuR regulatory axis contributes to tumourigenesis in colorectal cancer. Mol Cancer 17(1):11

    Article  Google Scholar 

  • Nakada M, Nakamura H, Ikeda E, Fujimoto N, Yamashita J, Sato H, Seiki M, Okada Y (1999) Expression and tissue localization of membrane-type 1, 2, and 3 matrix metalloproteinases in human astrocytic tumors. Am J Pathol 154(2):417–428

    Article  CAS  Google Scholar 

  • Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, Inamura K, Kim SA, Kuchiba A, Yamauchi M, Imamura Y, Willett WC, Rosner BA, Fuchs CS, Giovannucci E, Ogino S, Chan AT (2013) Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 369(12):1095–1105

    Article  CAS  Google Scholar 

  • Pan H, Hong Y, Yu B, Li L, Zhang X (2019) miR-4429 inhibits tumor progression and epithelial-mesenchymal transition via targeting CDK6 in clear cell renal cell carcinoma. Cancer Biother Radiopharm 34(5):334–341

    Article  CAS  Google Scholar 

  • Ren F, Tang R, Zhang X, Madushi WM, Luo D, Dang Y, Li Z, Wei K, Chen G (2015) Overexpression of MMP family members functions as prognostic biomarker for breast cancer patients: a systematic review and meta-analysis. PLoS One 10(8):e0135544

    Article  Google Scholar 

  • Rowe RG, Weiss SJ (2008) Breaching the basement membrane: who, when and how? Trends Cell Biol 18(11):560–574

    Article  CAS  Google Scholar 

  • Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S, Ostos LC, Lannon WA, Grotzinger C, Del Rio M, Lhermitte B, Olshen AB, Wiedenmann B, Cantley LC, Gray JW, Hanahan D (2013) A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 19(5):619–625

    Article  CAS  Google Scholar 

  • Shen Z, Wang X, Yu X, Zhang Y, Qin L (2017) MMP16 promotes tumor metastasis and indicates poor prognosis in hepatocellular carcinoma. Oncotarget 8(42):72197–72204

    Article  Google Scholar 

  • Shinkai K, Nakano K, Cui L, Mizuuchi Y, Onishi H, Oda Y, Obika S, Tanaka M, Katano M (2016) Nuclear expression of Y-box binding protein-1 is associated with poor prognosis in patients with pancreatic cancer and its knockdown inhibits tumor growth and metastasis in mice tumor models. Int J Cancer 139(2):433–445

    Article  CAS  Google Scholar 

  • Song H, Li Y, Lee J, Schwartz AL, Bu G (2009) Low-density lipoprotein receptor-related protein 1 promotes cancer cell migration and invasion by inducing the expression of matrix metalloproteinases 2 and 9. Cancer Res 69(3):879–886

    Article  CAS  Google Scholar 

  • Sun H, Fan G, Deng C, Wu L (2020) miR-4429 sensitized cervical cancer cells to irradiation by targeting RAD51. J Cell Physiol 235(1):185–193

    Article  CAS  Google Scholar 

  • Tatti O, Gucciardo E, Pekkonen P, Holopainen T, Louhimo R, Repo P, Maliniemi P, Lohi J, Rantanen V, Hautaniemi S, Alitalo K, Ranki A, Ojala PM, Keski-Oja J, Lehti K (2015) MMP16 mediates a proteolytic switch to promote cell-cell adhesion, collagen alignment, and lymphatic invasion in melanoma. Cancer Res 75(10):2083–2094

    Article  CAS  Google Scholar 

  • Wang H, Li XT, Wu C, Wu ZW, Li YY, Yang TQ, Chen GL, Xie XS, Huang YL, Du ZW, Zhou YX (2015) miR-132 can inhibit glioma cells invasion and migration by target MMP16 in vitro. Onco Targets Ther 8:3211–3218

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wu S, Ma C, Shan S, Zhou L, Li W (2017) High expression of matrix metalloproteinases 16 is associated with the aggressive malignant behavior and poor survival outcome in colorectal carcinoma. Sci Rep 7:46531

    Article  CAS  Google Scholar 

  • Wu WJ, Yin H, Hu JJ, Wei XZ (2018) Long noncoding RNA LINC00313 modulates papillary thyroid cancer tumorigenesis via sponging miR-4429. Neoplasma 65(6):933–942

    Article  CAS  Google Scholar 

  • Xu M, Chen X, Lin K, Zeng K, Liu X, Pan B, Xu X, Xu T, Hu X, Sun L, He B, Pan Y, Sun H, Wang S (2018) The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p. Mol Cancer 17(1):141

    Article  Google Scholar 

  • Xu XT, Xu Q, Tong JL, Zhu MM, Nie F, Chen X, Xiao SD, Ran ZH (2012) MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer. Br J Cancer 106(7):1320–1330

    Article  CAS  Google Scholar 

  • Zeng K, Chen X, Xu M, Liu X, Hu X, Xu T, Sun H, Pan Y, He B, Wang S (2018) CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis 9(4):417

    Article  Google Scholar 

  • Zhang Y, Wang Y, Wei Y, Li M, Yu S, Ye M, Zhang H, Chen S, Liu W, Zhang J (2015) MiR-129-3p promotes docetaxel resistance of breast cancer cells via CP110 inhibition. Sci Rep 5:15424

    Article  CAS  Google Scholar 

  • Zhu YM, Chen P, Shi L, Zhu T, Chen X (2020) MiR-4429 suppresses the malignant development of ovarian cancer by targeting YOD1. Eur Rev Med Pharmacol Sci 24(17):8722–8730

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Wei Li and Liang Wang contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Wei Li, Zhe Song, Nan Jia, and Cui Zhang. The first draft of the manuscript was written by Wei Li. Weina Gao and Liang Wang contributed reagents, materials, and analysis tools. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Liang Wang.

Ethics declarations

Conflict of interest

The authors declare they have no conflict of interest.

Additional information

Editor: Tetsuji Okamoto

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, W., Song, Z., Jia, N. et al. microRNA-4429-5p suppresses the malignant development of colon cancer by targeting matrix metalloproteinase 16. In Vitro Cell.Dev.Biol.-Animal 57, 715–725 (2021). https://doi.org/10.1007/s11626-021-00603-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-021-00603-4

Keywords

Navigation