Downregulation of microRNA-155 accelerates cell growth and invasion by targeting c-myc in human gastric carcinoma cells

Sun,Shibo; Sun,Peng; Wang,Chunmei; Sun,Tiewei

doi:10.3892/or.2014.3288

Downregulation of microRNA-155 accelerates cell growth and invasion by targeting c-myc in human gastric carcinoma cells

Authors:
- Shibo Sun
- Peng Sun
- Chunmei Wang
- Tiewei Sun
View Affiliations

Affiliations: Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China, Department of Animal Biology, Northeast Agricultural University, Harbin, Heilongjiang 150001, P.R. China
Published online on: June 24, 2014 https://doi.org/10.3892/or.2014.3288
Pages: 951-956

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

MicroRNAs (miRNAs) are a recently discovered class of small non-coding RNAs that regulate gene expression. miRNAs can contribute to cancer development and progression and are differentially expressed in normal tissue and cancer. In the present study, our aim was to investigate the expression of miR-155 in gastric cancer and to explore the mechanisms by which it influences gastric cancer cells. The level of miR-155 in 52 gastric carcinoma and corresponding non-tumor tissues was quantified by real-time reverse transcriptase-polymerase chain reaction. We used the data from EdU, CASY and cell adhesion assays to show how the expression of miR-155 affects viability and proliferation in SGC-7901 cancer cells. We also performed functional assays using the 3'-untranslated region (3'-UTR) of the c-myc gene as a miR-155 target in a luciferase reporter assay system. Our results indicated that miR-155 is downregulated in both human gastric carcinoma tissues and SGC-7901 cells. The high expression level of miR-155 may significantly downregulate cancer cell viability, proliferation and attachment. The level of miR-155 could influence endogenous c-myc expression in SGC-7901 cells, and may decrease its expression by binding to 3'-UTR of c-myc. In conclusion, our results suggest that miR-155 is extensively involved in the cancer pathogenesis of gastric carcinoma and support its function as recessive cancer genes. c-myc is an important miR-155 target gene.

View Figures

View References

1	Ambros V: MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell. 113:673–676. 2003. View Article : Google Scholar : PubMed/NCBI
2	Cullen BR: Transcription and processing of human microRNA precursors. Mol Cell. 16:861–865. 2004. View Article : Google Scholar : PubMed/NCBI
3	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
4	Eder M and Scherr M: MicroRNA and lung cancer. N Engl J Med. 352:2446–2448. 2005. View Article : Google Scholar : PubMed/NCBI
5	Ma L, Teruya-Feldstein J and Weinberg RA: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 449:682–688. 2007. View Article : Google Scholar : PubMed/NCBI
6	Ji J, Shi J, Budhu A, et al: MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 361:1437–1447. 2009. View Article : Google Scholar : PubMed/NCBI
7	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar
8	Hammond SM: MicroRNAs as oncogenes. Curr Opin Genet Dev. 16:4–9. 2006. View Article : Google Scholar
9	Calin GA, Sevignani C, Dumitru CD, et al: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI
10	Zhang L, Huang J, Yang N, et al: microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci USA. 103:9136–9141. 2006. View Article : Google Scholar : PubMed/NCBI
11	Iorio MV, Ferracin M, Liu CG, et al: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65:7065–7070. 2005. View Article : Google Scholar : PubMed/NCBI
12	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
13	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
14	Yanaihara N, Caplen N, Bowman E, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9:189–198. 2006. View Article : Google Scholar : PubMed/NCBI
15	Nam EJ, Yoon H, Kim SW, et al: MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res. 14:2690–2695. 2008. View Article : Google Scholar : PubMed/NCBI
16	He L, Thomson JM, Hemann MT, et al: A microRNA polycistron as a potential human oncogene. Nature. 435:828–833. 2005. View Article : Google Scholar : PubMed/NCBI
17	Zheng SR, Guo GL, Zhai Q, et al: Effects of miR-155 antisense oligonucleotide on breast carcinoma cell line MDA-MB-157 and implanted tumors. Asian Pac J Cancer Prev. 14:2361–2366. 2013. View Article : Google Scholar : PubMed/NCBI
18	Pu J, Bai D, Yang X, et al: Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155. Biochem Biophys Res Commun. 428:210–215. 2012. View Article : Google Scholar : PubMed/NCBI
19	Sinha AU, Kaimal V, Chen J and Jegga AG: Dissecting microregulation of a master regulatory network. BMC Genomics. 9:882008. View Article : Google Scholar : PubMed/NCBI
20	Kolesnikov NN, Titov SE, Veriaskina IA, et al: MicroRNA, evolution and cancer. Tsitologiia. 55:159–164. 2013.(In Russian).
21	Hede K: Studies define role of microRNA in cancer. J Natl Cancer Inst. 97:1114–1115. 2005. View Article : Google Scholar : PubMed/NCBI
22	Gregory RI and Shiekhattar R: MicroRNA biogenesis and cancer. Cancer Res. 65:3509–3512. 2005. View Article : Google Scholar : PubMed/NCBI
23	Chen C, Ridzon DA, Broomer AJ, et al: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI
24	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
25	Yu Y, Arora A, Min W, et al: EdU incorporation is an alternative non-radioactive assay to [³H]thymidine uptake for in vitro measurement of mice T-cell proliferations. J Immunol Methods. 350:29–35. 2009.
26	Diermeier-Daucher S, Clarke ST, Hill D, et al: Cell type specific applicability of 5-ethynyl-2′-deoxyuridine (EdU) for dynamic proliferation assessment in flow cytometry. Cytometry A. 75:535–546. 2009.PubMed/NCBI
27	Kohlmeier F, Maya-Mendoza A and Jackson DA: EdU induces DNA damage response and cell death in mESC in culture. Chromosome Res. 21:87–100. 2013. View Article : Google Scholar : PubMed/NCBI
28	Schwarzenbacher D, Balic M and Pichler M: The role of microRNAs in breast cancer stem cells. Int J Mol Sci. 14:14712–14723. 2013. View Article : Google Scholar : PubMed/NCBI
29	Wang L, Jia XJ, Jiang HJ, et al: MicroRNAs 185, 96, and 223 repress selective high-density lipoprotein cholesterol uptake through posttranscriptional inhibition. Mol Cell Biol. 33:1956–1964. 2013. View Article : Google Scholar
30	Yasui W, Yokozaki H, Fujimoto J, et al: Genetic and epigenetic alterations in multistep carcinogenesis of the stomach. J Gastroenterol. 35(Suppl 12): 111–115. 2000.PubMed/NCBI
31	Tahara E: Molecular biology of gastric cancer. World J Surg. 19:484–490. 1995. View Article : Google Scholar
32	Liu Y, Xing R, Zhang X, et al: miR-375 targets the p53 gene to regulate cellular response to ionizing radiation and etoposide in gastric cancer cells. DNA Repair. 12:741–750. 2013. View Article : Google Scholar : PubMed/NCBI
33	Yang TS, Yang XH, Wang XD, et al: MiR-214 regulate gastric cancer cell proliferation, migration and invasion by targeting PTEN. Cancer Cell Int. 13:682013. View Article : Google Scholar : PubMed/NCBI
34	Sacconi A, Biagioni F, Canu V, et al: miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer. Cell Death Dis. 3:e4232012. View Article : Google Scholar : PubMed/NCBI
35	Sun T, Wang C, Xing J and Wu D: miR-429 modulates the expression of c-myc in human gastric carcinoma cells. Eur J Cancer. 47:2552–2559. 2011. View Article : Google Scholar : PubMed/NCBI
36	Voorhoeve PM and Agami R: Classifying microRNAs in cancer: the good, the bad and the ugly. Biochim Biophys Acta. 1775:274–282. 2007.PubMed/NCBI
37	Xie Q, Chen X, Lu F, et al: Aberrant expression of microRNA 155 may accelerate cell proliferation by targeting sex-determining region Y box 6 in hepatocellular carcinoma. Cancer. 118:2431–2442. 2012. View Article : Google Scholar : PubMed/NCBI
38	Eilers M and Eisenman RN: Myc’s broad reach. Genes Dev. 22:2755–2766. 2008.
39	Chen Z, Zeng H, Guo Y, et al: miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc. J Exp Clin Cancer Res. 29:1512010. View Article : Google Scholar : PubMed/NCBI
40	Sachdeva M, Zhu S, Wu F, et al: p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci USA. 106:3207–3212. 2009. View Article : Google Scholar : PubMed/NCBI
41	Tibshirani R, Hastie T, Narasimhan B and Chu G: Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc Natl Acad Sci USA. 99:6567–6572. 2002. View Article : Google Scholar : PubMed/NCBI
42	Johnson SM, Grosshans H, Shingara J, et al: RAS is regulated by the let-7 microRNA family. Cell. 120:635–647. 2005. View Article : Google Scholar
43	O’Donnell KA, Wentzel EA, Zeller KI, et al: c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 435:839–843. 2005.PubMed/NCBI
44	Cimmino A, Calin GA, Fabbri M, et al: miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 102:13944–13949. 2005. View Article : Google Scholar
45	Krützfeldt J, Rajewsky N, Braich R, et al: Silencing of microRNAs in vivo with ‘antagomirs’. Nature. 438:685–689. 2005.
46	Meister G and Tuschl T: Mechanisms of gene silencing by double-stranded RNA. Nature. 431:343–349. 2004. View Article : Google Scholar : PubMed/NCBI