miR-300 promotes proliferation and EMT-mediated colorectal cancer migration and invasion by targeting p53

Wang,Lin; Yu,Peiwu

doi:10.3892/or.2016.5193

miR-300 promotes proliferation and EMT-mediated colorectal cancer migration and invasion by targeting p53

Authors:
- Lin Wang
- Peiwu Yu
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Affiliations: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, The Third Military Medical University, Shapingba, Chongqing 400038, P.R. China
Published online on: October 21, 2016 https://doi.org/10.3892/or.2016.5193
Pages: 3225-3232

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Abstract

p53 mutations in tumors can induce the loss of wild-type tumor-suppressing p53 function, which results in the increase in proliferation, migration and invasion ability in cancer cells. Studies have shown that the expression of p53 is regulated by several microRNAs (miRNAs). In the present study, we found that miR-300 and p53 were significantly increased in colorectal cancer (CRC) tissues when compared with levels noted in adjacent colorectal tissues. Both miR-300 and p53 were significantly correlated with lymphatic metastasis and TNM stage. Both miR-300 and p53 promoted CRC cell (SW480 and HT29) proliferation, migration, and invasion, respectively, in vitro. In addition, we found that miR-300 is a direct positive regulator of p53 through binding to the binding site in the 3'UTR of the p53 gene in human CRC cells. Moreover, both miR-300 and p53 induced CRC cell epithelial‑mesenchymal transition (EMT) respectively. Taken together, we demonstrated that miR-300 promoted proliferation and EMT-mediated CRC migration and invasion by targeting p53. These findings provide a new theoretical basis and potential therapeutic targets, and thus lays the foundation for exploring the pathogenesis of CRC.

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1	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
2	Boyle P and Langman JS: ABC of colorectal cancer: Epidemiology. BMJ. 321:805–808. 2000. View Article : Google Scholar : PubMed/NCBI
3	Glade MJ: Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997. Nutrition. 15:523–526. 1999.PubMed/NCBI
4	Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014. View Article : Google Scholar : PubMed/NCBI
5	Muller PA and Vousden KH: Mutant p53 in cancer: New functions and therapeutic opportunities. Cancer Cell. 25:304–317. 2014. View Article : Google Scholar : PubMed/NCBI
6	Wang Y, Suh Y-A, Fuller MY, Jackson JG, Xiong S, Terzian T, Quintás-Cardama A, Bankson JA, El-Naggar AK and Lozano G: Restoring expression of wild-type p53 suppresses tumor growth but does not cause tumor regression in mice with a p53 missense mutation. J Clin Invest. 121:893–904. 2011. View Article : Google Scholar : PubMed/NCBI
7	Hollstein M, Sidransky D, Vogelstein B and Harris CC: p53 mutations in human cancers. Science. 253:49–53. 1991. View Article : Google Scholar : PubMed/NCBI
8	Creighton CJ, Gibbons DL and Kurie JM: The role of epithelial-mesenchymal transition programming in invasion and metastasis: A clinical perspective. Cancer Manag Res. 5:187–195. 2013. View Article : Google Scholar : PubMed/NCBI
9	Lamouille S, Xu J and Derynck R: Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 15:178–196. 2014. View Article : Google Scholar : PubMed/NCBI
10	Sheppard D: Epithelial-mesenchymal interactions in fibrosis and repair. Transforming growth factor-β activation by epithelial cells and fibroblasts. Ann Am Thorac Soc. 12:(Suppl 1). S21–S23. 2015. View Article : Google Scholar : PubMed/NCBI
11	Kovacic JC, Mercader N, Torres M, Boehm M and Fuster V: Epithelial-to-mesenchymal and endothelial-to-mesenchymal transition: From cardiovascular development to disease. Circulation. 125:1795–1808. 2012. View Article : Google Scholar : PubMed/NCBI
12	Fraga CH, True LD and Kirk D: Enhanced expression of the mesenchymal marker, vimentin, in hyperplastic versus normal human prostatic epithelium. J Urol. 159:270–274. 1998. View Article : Google Scholar : PubMed/NCBI
13	Jiang L, Lai YK, Zhang J, Wang H, Lin MC, He ML and Kung HF: Targeting S100P inhibits colon cancer growth and metastasis by lentivirus-mediated RNA interference and proteomic analysis. Mol Med. 17:709–716. 2011. View Article : Google Scholar : PubMed/NCBI
14	Jiang L, Chen Y, Chan CY, Wang X, Lin L, He ML, Lin MC, Yew DT, Sung JJ, Li JC, et al: Down-regulation of stathmin is required for TGF-beta inducible early gene 1 induced growth inhibition of pancreatic cancer cells. Cancer Lett. 274:101–108. 2009. View Article : Google Scholar : PubMed/NCBI
15	Peacock O, Lee AC, Cameron F, Tarbox R, Vafadar-Isfahani N, Tufarelli C and Lund JN: Inflammation and MiR-21 pathways functionally interact to downregulate PDCD4 in colorectal cancer. PLoS One. 9:e1102672014. View Article : Google Scholar : PubMed/NCBI
16	Zhang J, Fei B, Wang Q, Song M, Yin Y, Zhang B, Ni S, Guo W, Bian Z, Quan C, et al: MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma. Oncotarget. 5:12083–12096. 2014. View Article : Google Scholar : PubMed/NCBI
17	Wang J, Paris PL, Chen J, Ngo V, Yao H, Frazier ML, Killary AM, Liu CG, Liang H, Mathy C, et al: Next generation sequencing of pancreatic cyst fluid microRNAs from low grade-benign and high grade-invasive lesions. Cancer Lett. 356:404–409. 2015. View Article : Google Scholar : PubMed/NCBI
18	Kasinski AL and Slack FJ: Epigenetics and genetics. MicroRNAs en route to the clinic: Progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 11:849–864. 2011. View Article : Google Scholar : PubMed/NCBI
19	Stahlhut C and Slack FJ: MicroRNAs and the cancer phenotype: Profiling, signatures and clinical implications. Genome Med. 5:1112013. View Article : Google Scholar : PubMed/NCBI
20	Friedman RC, Farh KK-H, Burge CB and Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19:92–105. 2009. View Article : Google Scholar : PubMed/NCBI
21	Christofori G: New signals from the invasive front. Nature. 441:444–450. 2006. View Article : Google Scholar : PubMed/NCBI
22	Berx G, Raspé E, Christofori G, Thiery JP and Sleeman JP: Pre-EMTing metastasis? Recapitulation of morphogenetic processes in cancer. Clin Exp Metastasis. 24:587–597. 2007. View Article : Google Scholar : PubMed/NCBI
23	Huber MA, Kraut N and Beug H: Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 17:548–558. 2005. View Article : Google Scholar : PubMed/NCBI
24	Lee JM, Dedhar S, Kalluri R and Thompson EW: The epithelial-mesenchymal transition: New insights in signaling, development, and disease. J Cell Biol. 172:973–981. 2006. View Article : Google Scholar : PubMed/NCBI
25	Schipper JH, Frixen UH, Behrens J, Unger A, Jahnke K and Birchmeier W: E-cadherin expression in squamous cell carcinomas of head and neck: Inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res. 51:6328–6337. 1991.PubMed/NCBI
26	Oka H, Shiozaki H, Kobayashi K, Inoue M, Tahara H, Kobayashi T, Takatsuka Y, Matsuyoshi N, Hirano S, Takeichi M, et al: Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 53:1696–1701. 1993.PubMed/NCBI
27	Perl A-K, Wilgenbus P, Dahl U, Semb H and Christofori G: A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature. 392:190–193. 1998. View Article : Google Scholar : PubMed/NCBI
28	Vleminckx K, Vakaet L Jr, Mareel M, Fiers W and van Roy F: Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 66:107–119. 1991. View Article : Google Scholar : PubMed/NCBI
29	Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Löchner D and Birchmeier W: E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 113:173–185. 1991. View Article : Google Scholar : PubMed/NCBI
30	Gumbiner BM: Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol. 6:622–634. 2005. View Article : Google Scholar : PubMed/NCBI
31	Ivaska J, Vuoriluoto K, Huovinen T, Izawa I, Inagaki M and Parker PJ: PKCepsilon-mediated phosphorylation of vimentin controls integrin recycling and motility. EMBO J. 24:3834–3845. 2005. View Article : Google Scholar : PubMed/NCBI
32	Vuoriluoto K, Haugen H, Kiviluoto S, Mpindi JP, Nevo J, Gjerdrum C, Tiron C, Lorens JB and Ivaska J: Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer. Oncogene. 30:1436–1448. 2011. View Article : Google Scholar : PubMed/NCBI