MicroRNA-125b may function as an oncogene in lung cancer cells

Wang,Xikai; Zhang,Yanqiu; Fu,Yanyun; Zhang,Juan; Yin,Lihong; Pu,Yuepu; Liang,Geyu

doi:10.3892/mmr.2014.3142

MicroRNA-125b may function as an oncogene in lung cancer cells

Authors:
- Xikai Wang
- Yanqiu Zhang
- Yanyun Fu
- Juan Zhang
- Lihong Yin
- Yuepu Pu
- Geyu Liang
View Affiliations

Affiliations: Key Laboratory of Environmental Medicine Engineering Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, P.R. China
Published online on: December 31, 2014 https://doi.org/10.3892/mmr.2014.3142
Pages: 3880-3887

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to investigate the biofunctions of microRNA (miR)‑125b on lung cancer cells. A miR genechip array was used to examine the differential expression of miRs between 95D lung cancer cells and 16 human bronchial epithelial (HBE) cells. Overexpression of miR‑125b was observed in the cell lines and in the lung carcinoma tissues compared with the adjacent tissues, confirmed using reverse transcription quantitative polymerase chain reaction. Bioinformatic analysis of miR‑125b was also performed, including target prediction, gene ontology and pathway analysis. MTT, flow cytometry and Transwell assays were also used to examine the effect of downregulated miR‑125b on the proliferation, apoptosis, invasive ability and cell cycle of 95D cells. Significant differences were observed in the expression of 45 miRs in the 95D cells compared with those in 16HBE cells and the expression of miR‑125b was significantly higher in 95D cells compared with that in 16HBE cells as well as in lung tumor tissues compared with that in adjacent tissues. In addition, inhibition of the expression of miR‑125b in 95D cells induced apoptosis, G1/S phase arrest and reduction of their invasive ability. In addition, bioinformatics software predicted that miR‑125b was involved in the regulation of several pathways associated with cancer, including the transforming growth factor‑β, Wnt and mitogen‑activated protein kinase signaling pathways. These data indicated for the first time, to the best of our knowledge, that miR‑125b may function as an oncogene in lung cancer.

View Figures

View References

1	Lee RC, Feinbaum RL and Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993. View Article : Google Scholar : PubMed/NCBI
2	Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR and Ruvkun G: The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 403:901–906. 2000. View Article : Google Scholar : PubMed/NCBI
3	Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F and Croce CM: Frequent deletions and down-regulation of microRNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 99:15524–15529. 2002. View Article : Google Scholar
4	Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T and Takahashi T: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64:3753–3756. 2004. View Article : Google Scholar : PubMed/NCBI
5	Michael MZ, O’Connor SM, van Holst Pellekaan NG, Young GP and James RJ: Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 1:882–891. 2003.PubMed/NCBI
6	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar
7	Frezzetti D, De Menna M and Zoppoli P: Upregulation of miR-21 by Ras in vivo and its role in tumor growth. Oncogene. 30:275–286. 2011. View Article : Google Scholar
8	Yuxia M, Zhennan T and Wei Z: Circulating miR-125b is a novel biomarker for screening non-small-cell lung cancer and predicts poor prognosis. J Cancer Res Clin Oncol. 138:2045–2050. 2012. View Article : Google Scholar : PubMed/NCBI
9	Li Y, Chao Y, Fang Y, Wang J, Wang M, Zhang H, Ying M, Zhu XX and Wang HF: MTA1 promotes the invasion and migration of non-small cell lung cancer cells by downregulating miR-125b. J Exp Clin Cancer Res. 32:332013. View Article : Google Scholar : PubMed/NCBI
10	Nishida N, Yokobori T, Mimori K, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Kuwano H and Mori M: MicroRNA miR-125b is a prognostic marker in human colorectal cancer. Int J Oncol. 38:1437–1443. 2011.PubMed/NCBI
11	Pang Y, Young CY and Yuan H: MicroRNAs and prostate cancer. Acta Biochim Biophys Sin (Shanghai). 42:363–369. 2010. View Article : Google Scholar
12	Bousquet M, Harris MH, Zhou B and Lodish HF: MicroRNA miR-125b causes leukemia. Proc Natl Acad Sci USA. 107:21558–21563. 2010. View Article : Google Scholar : PubMed/NCBI
13	Dang XM, Ma AQ, Yang L, Hu H, Zhu B, Shang D, Chen TJ and Luo Y: MicroRNA-26a regulates tumorigenic properties of EZH2 in human lung carcinoma cells. Cancer Genet. 205:113–123. 2012. View Article : Google Scholar : PubMed/NCBI
14	Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-β family signaling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI
15	Bacon AL, Farrington SM and Dunlop MG: Mutation frequency in coding and non-coding repeat sequences in mismatch repair deficient cells derived from normal human tissue. Oncogene. 20:7464–7471. 2001. View Article : Google Scholar : PubMed/NCBI
16	Johnson GL and Lapadat R: Mitogen activated protein kinases pathways mediated by ERK, JNK, and p38 protein kinases. Science. 298:1911–1912. 2002. View Article : Google Scholar : PubMed/NCBI
17	Stacey DW: Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells. Curr Opin Cell Biol. 15:158–163. 2003. View Article : Google Scholar : PubMed/NCBI
18	Kranenburg O, Gebbink MF and Voest EE: Stimulation of angiogenesis by Ras proteins. Biochim Biophys Acta. 1654:23–37. 2004.PubMed/NCBI
19	Wagner EF and Nebreda AR: Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 9:537–549. 2009. View Article : Google Scholar : PubMed/NCBI
20	Weston CR and Davis RJ: The JNK signal transduction pathway. Curr Opin Cell Biol. 12:14–21. 2002.
21	Cheung PC, Campbell DG, Nebreda AR and Cohen P: Feedback control of the protein kinase TAK1 by SAPK2a/p38α. EMBO J. 22:5793–5805. 2003. View Article : Google Scholar : PubMed/NCBI
22	Van SM, Randall J, Sorgew A, Williams LM, Tennis M and Winn RA: Wnt signaling pathway and lung disease. Transl Res. 151:175–180. 2008. View Article : Google Scholar
23	Shi XB, Xue L, Yang J, Ma AH, Zhao J, Xu M, Tepper CG, Evans CP, Kung HJ and deVere White RW: An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells. Proc Natl Acad Sci USA. 104:19983–19988. 2007. View Article : Google Scholar : PubMed/NCBI
24	Xia HF, He TZ, Liu CM, Cui Y, Song PP, Jin XH and Ma X: MiR-125b expression affects the proliferation and apoptosis of human glioma cells by targeting Bmf. Cell Physiol Biochem. 23:347–358. 2009. View Article : Google Scholar : PubMed/NCBI
25	Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS and Benz CC: Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem. 282:1479–1486. 2007. View Article : Google Scholar
26	Liang L, Wong CM, Ying Q, Fan DN, Huang S, Ding J, Yao J, Yan M, Li J, Yao M, Ng IO and He X: MicroRNA-125b suppresses human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2. Hepatology. 52:1731–1740. 2010. View Article : Google Scholar : PubMed/NCBI