miR‑494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN

Sun,Hai‑Bing; Chen,Xi; Ji,Hong; Wu,Tao; Lu,Hong‑Wei; Zhang,Yan; Li,Hua; Li,Yi‑Ming

doi:10.3892/ijo.2014.2665

miR‑494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN

Authors:
- Hai‑Bing Sun
- Xi Chen
- Hong Ji
- Tao Wu
- Hong‑Wei Lu
- Yan Zhang
- Hua Li
- Yi‑Ming Li
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Affiliations: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
Published online on: September 22, 2014 https://doi.org/10.3892/ijo.2014.2665
Pages: 2486-2494

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Abstract

Accumulating evidence has shown that microRNAs (miRNAs) are involved in multiple processes in cancer development and progression. Upregulation of miRNA‑494 (miR‑494) has been identified as an oncogenic miRNA and is associated with poor prognosis in several types of human cancer. However, the specific function of miR‑494 in colorectal cancer remains unclear. In this study we found that the expression of miR‑494 in colorectal cancer tissues and cell lines was much higher than in normal control tissues and cells, respectively. In addition, upregulation of miR‑494 more frequently occurred in tissue specimens with adverse clinical stage and the presence of distant metastasis. Moreover, multivariate survival analyses demonstrated that overexpression of miR‑494 is an independent prognostic factor for both progression‑free and overall survival. In addition miR‑494 promoted invasion and migration in colorectal cancer cells, and miR‑494 directly inhibited the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression by targeting its 3'‑untranslated region (3'‑UTR). Moreover, PTEN is down regulated and inversely correlated with miR‑494 expression in tissues. Thus, for the first time, we provided convincing evidence that upregulation of miR‑494 was associated with tumor aggressiveness and tumor metastasis and promoted cell migration and invasion by targeting PTEN gene in colorectal cancer, and miR‑494 is an independent prognostic marker for colorectal cancer patients.

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1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar
2	van den Berg A, Mols J and Han J: RISC-target interaction: cleavage and translational suppression. Biochim Biophys Acta. 1779:668–677. 2008.PubMed/NCBI
3	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
4	Kumar MS, Lu J, Mercer KL, Golub TR and Jacks T: Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 39:673–677. 2007. View Article : Google Scholar : PubMed/NCBI
5	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
6	Croce CM and Calin GA: miRNAs, cancer, and stem cell division. Cell. 122:6–7. 2005. View Article : Google Scholar : PubMed/NCBI
7	Gregory RI and Shiekhattar R: MicroRNA biogenesis and cancer. Cancer Res. 65:3509–3512. 2005. View Article : Google Scholar
8	Lu J, Getz G, Miska EA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
9	Volinia S, Calin GA, Liu CG, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:2257–2261. 2006. View Article : Google Scholar : PubMed/NCBI
10	Lujambio A, Calin GA, Villanueva A, et al: A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA. 105:13556–13561. 2008. View Article : Google Scholar : PubMed/NCBI
11	Ma Y, Zhang P, Wang F, et al: miR-150 as a potential biomarker associated with prognosis and therapeutic outcome in colorectal cancer. Gut. 61:1447–1453. 2012. View Article : Google Scholar : PubMed/NCBI
12	Almeida MI, Nicoloso MS, Zeng L, et al: Strand-specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells. Gastroenterology. 142:886–896. e92012. View Article : Google Scholar : PubMed/NCBI
13	Pichler M, Ress AL, Winter E, et al: MiR-200a regulates epithelial to mesenchymal transition-related gene expression and determines prognosis in colorectal cancer patients. Br J Cancer. 110:1614–1621. 2014. View Article : Google Scholar : PubMed/NCBI
14	Hwang WL, Jiang JK, Yang SH, et al: MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells. Nat Cell Biol. 16:268–280. 2014. View Article : Google Scholar : PubMed/NCBI
15	Yang X, Zeng Z, Hou Y, et al: MicroRNA-92a as a potential biomarker in diagnosis of colorectal cancer: a systematic review and meta-analysis. PLoS One. 9:e887452014. View Article : Google Scholar : PubMed/NCBI
16	Liu Y, Zhou Y, Feng X, et al: Low expression of microRNA-126 is associated with poor prognosis in colorectal cancer. Genes Chromosomes Cancer. 53:358–365. 2014. View Article : Google Scholar : PubMed/NCBI
17	Zhao JJ, Yang J, Lin J, et al: Identification of miRNAs associated with tumorigenesis of retinoblastoma by miRNA microarray analysis. Childs Nerv Syst. 25:13–20. 2009. View Article : Google Scholar : PubMed/NCBI
18	Shen YL, Jiang YG, Greenlee AR, Zhou LL and Liu LH: MicroRNA expression profiles and miR-10a target in anti-benzo[a] pyrene-7, 8-diol-9, 10-epoxide-transformed human 16HBE cells. Biomed Environ Sci. 22:14–21. 2009.PubMed/NCBI
19	Liu Y, Lai L, Chen Q, et al: MicroRNA-494 is required for the accumulation and functions of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN. J Immunol. 188:5500–5510. 2012. View Article : Google Scholar : PubMed/NCBI
20	Kwak SY, Yang JS, Kim BY, Bae IH and Han YH: Ionizing radiation-inducible miR-494 promotes glioma cell invasion through EGFR stabilization by targeting p190B rhoGAP. Biochim Biophys Acta. 1843:508–516. 2014. View Article : Google Scholar : PubMed/NCBI
21	Yamanaka S, Campbell NR, An F, et al: Coordinated effects of microRNA-494 induce G₂/M arrest in human cholangiocarcinoma. Cell Cycle. 11:2729–2738. 2012. View Article : Google Scholar : PubMed/NCBI
22	Olaru AV, Ghiaur G, Yamanaka S, et al: MicroRNA downregulated in human cholangiocarcinoma control cell cycle through multiple targets involved in the G1/S checkpoint. Hepatology. 54:2089–2098. 2011. View Article : Google Scholar : PubMed/NCBI
23	Li X, Luo F, Li Q, et al: Identification of new aberrantly expressed miRNAs in intestinal-type gastric cancer and its clinical significance. Oncol Rep. 26:1431–1439. 2011.PubMed/NCBI
24	Leibovitz A, Stinson JC, McCombs WB 3rd, McCoy CE, Mazur KC and Mabry ND: Classification of human colorectal adenocarcinoma cell lines. Cancer Res. 36:4562–4569. 1976.PubMed/NCBI
25	Sawai H, Yasuda A, Ochi N, et al: Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival. BMC Gastroenterol. 8:562008. View Article : Google Scholar : PubMed/NCBI
26	Bowen KA, Doan HQ, Zhou BP, et al: PTEN loss induces epithelial-mesenchymal transition in human colon cancer cells. Anticancer Res. 29:4439–4449. 2009.PubMed/NCBI
27	Liu L, Jiang Y, Zhang H, Greenlee AR and Han Z: Overexpressed miR-494 down-regulates PTEN gene expression in cells transformed by anti-benzo(a)pyrene-trans-7,8-dihydrodiol- 9,10-epoxide. Life Sci. 86:192–198. 2010. View Article : Google Scholar : PubMed/NCBI
28	Ohdaira H, Sekiguchi M, Miyata K and Yoshida K: Micro-RNA-494 suppresses cell proliferation and induces senescence in A549 lung cancer cells. Cell Prolif. 45:32–38. 2012. View Article : Google Scholar : PubMed/NCBI
29	Lim L, Balakrishnan A, Huskey N, et al: MicroRNA-494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer. Hepatology. 59:202–215. 2014. View Article : Google Scholar : PubMed/NCBI
30	Romano G, Acunzo M, Garofalo M, et al: MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small-cell lung cancer through BIM down-regulation. Proc Natl Acad Sci USA. 109:16570–16575. 2012. View Article : Google Scholar : PubMed/NCBI
31	Molinari F and Frattini M: Functions and regulation of the PTEN gene in colorectal cancer. Front Oncol. 3:3262014. View Article : Google Scholar : PubMed/NCBI
32	Sansal I and Sellers WR: The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol. 22:2954–2963. 2004. View Article : Google Scholar : PubMed/NCBI
33	Castellino RC and Durden DL: Mechanisms of disease: the PI3K-Akt-PTEN signaling node - an intercept point for the control of angiogenesis in brain tumors. Nat Clin Pract Neurol. 3:682–693. 2007. View Article : Google Scholar : PubMed/NCBI
34	Grille SJ, Bellacosa A, Upson J, et al: The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 63:2172–2178. 2003.
35	Vogt PK, Gymnopoulos M and Hart JR: PI 3-kinase and cancer: changing accents. Curr Opin Genet Dev. 19:12–17. 2009. View Article : Google Scholar : PubMed/NCBI
36	Zhang S and Yu D: PI(3)king apart PTEN’s role in cancer. Clin Cancer Res. 16:4325–4330. 2010.PubMed/NCBI
37	Song MS, Salmena L and Pandolfi PP: The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 13:283–296. 2012.PubMed/NCBI
38	Stewart AL, Mhashilkar AM, Yang XH, et al: PI3 kinase blockade by Ad-PTEN inhibits invasion and induces apoptosis in RGP and metastatic melanoma cells. Mol Med. 8:451–461. 2002.PubMed/NCBI
39	Tamura M, Gu J, Matsumoto K, Aota S, Parsons R and Yamada KM: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science. 280:1614–1617. 1998. View Article : Google Scholar : PubMed/NCBI