Overexpression of Lin28 inhibits the proliferation, migration and cell cycle progression and induces apoptosis of BGC-823 gastric cancer cells

Song,Hu; Xu,Wei; Song,Jun; Liang,Yong; Fu,Wei; Zhu,Xiao‑Cheng; Li,Chao; Peng,Jun-Sheng; Zheng,Jun-Nian

doi:10.3892/or.2014.3674

Overexpression of Lin28 inhibits the proliferation, migration and cell cycle progression and induces apoptosis of BGC-823 gastric cancer cells

Authors:
- Hu Song
- Wei Xu
- Jun Song
- Yong Liang
- Wei Fu
- Xiao‑Cheng Zhu
- Chao Li
- Jun-Sheng Peng
- Jun-Nian Zheng
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Affiliations: Department of Gastrointestinal Surgery, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China, Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital (Gastrointestinal and Anal Hospital), Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China, Jiangsu Province Tumor Biological Therapy Institute, Xuzhou, Jiangsu 221000, P.R. China
Published online on: December 15, 2014 https://doi.org/10.3892/or.2014.3674
Pages: 997-1003

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Abstract

Lin28 plays important roles in the development, maintenance of pluripotency and progression of various types of cancers. Lin28 represses the biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Oncogenic regulation of let-7 microRNAs has been demonstrated in several human malignancies, yet their correlation with Lin28 has not yet been studied in gastric cancer. Therefore, in the present study, we explored the possible mechanisms involved in the effects by Lin28 on the proliferation, migration, cell cycle arrest and apoptosis in gastric cancer cells via alteration of let-7 miRNA. The expression levels of Lin28 and let-7 were detected by real-time PCR in gastric cancer cell lines in vitro. Lin28 was overexpressed in the BGC-823 cells via lentiviral transfection, and let-7 expression was assessed. Cell proliferation and migration capabilities were investigated by MTT and Transwell assays, while cell cycle distribution and the apoptosis rate were detected using flow cytometry. The expression of Lin28 was moderately expressed in the GES cells while underexpressed in the BGC-823, SGC-7901 and HGC-27 cells. Let-7a miRNA was highly expressed in the GES, BGC-823, SGC-7901 and HGC-27 cells. Overexpression of Lin28 was inversely correlated with the downregulated expression of let-7a, and markedly suppressed the proliferation, migration, cell cycle progression and induced apoptosis in the BGC-823 cells. These findings demonstrated that overexpression of Lin28 can suppress the biological behavior of gastric cancer in vitro, and let-7 miRNA may play an important role in the process. We suggest that Lin28 may be a candidate predictor or an anticancer therapeutic target for gastric cancer patients.

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1	Moss EG, Lee RC and Ambros V: The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell. 88:637–646. 1997. View Article : Google Scholar : PubMed/NCBI
2	Yu J, Vodyanik MA, Smuga-Otto K, et al: Induced pluripotent stem cell lines derived from human somatic cells. Science. 318:1917–1920. 2007. View Article : Google Scholar : PubMed/NCBI
3	West JA, Viswanathan SR, Yabuuchi A, et al: A role for Lin28 in primordial germ-cell development and germ-cell malignancy. Nature. 460:909–913. 2009.PubMed/NCBI
4	Wong SS, Ritner C, Ramachandran S, et al: miR-125b promotes early germ layer specification through Lin28/let-7d and preferential differentiation of mesoderm in human embryonic stem cells. PLoS One. 7:e361212012. View Article : Google Scholar : PubMed/NCBI
5	Gonzalez F, Barragan Monasterio M, Tiscornia G, et al: Generation of mouse-induced pluripotent stem cells by transient expression of a single nonviral polycistronic vector. Proc Natl Acad Sci USA. 106:8918–8922. 2009. View Article : Google Scholar : PubMed/NCBI
6	Thornton JE and Gregory RI: How does Lin28 let-7 control development and disease? Trends Cell Biol. 22:474–482. 2012. View Article : Google Scholar : PubMed/NCBI
7	Viswanathan SR, Powers JT, Einhorn W, et al: Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet. 41:843–848. 2009. View Article : Google Scholar : PubMed/NCBI
8	Guo Y, Chen Y, Ito H, Watanabe A, Ge X, Kodama T and Aburatani H: Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma. Gene. 384:51–61. 2006. View Article : Google Scholar : PubMed/NCBI
9	Saiki Y, Ishimaru S, Mimori K, et al: Comprehensive analysis of the clinical significance of inducing pluripotent stemness-related gene expression in colorectal cancer cells. Ann Surg Oncol. 16:2638–2644. 2009. View Article : Google Scholar : PubMed/NCBI
10	Pan L, Gong Z, Zhong Z, Dong Z, Liu Q, Le Y and Guo J: Lin-28 reactivation is required for let-7 repression and proliferation in human small cell lung cancer cells. Mol Cell Biochem. 355:257–263. 2011. View Article : Google Scholar : PubMed/NCBI
11	Heo I, Joo C, Cho J, Ha M, Han J and Kim VN: Lin28 mediates the terminal uridylation of let-7 precursor microRNA. Mol Cell. 32:276–284. 2008. View Article : Google Scholar : PubMed/NCBI
12	Newman MA, Thomson JM and Hammond SM: Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA. 14:1539–1549. 2008. View Article : Google Scholar : PubMed/NCBI
13	Rybak A, Fuchs H, Smirnova L, Brandt C, Pohl EE, Nitsch R and Wulczyn FG: A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nat Cell Biol. 10:987–993. 2008. View Article : Google Scholar : PubMed/NCBI
14	Viswanathan SR, Daley GQ and Gregory RI: Selective blockade of microRNA processing by Lin28. Science. 320:97–100. 2008. View Article : Google Scholar : PubMed/NCBI
15	Viswanathan SR and Daley GQ: Lin28: a microRNA regulator with a macro role. Cell. 140:445–449. 2010. View Article : Google Scholar : PubMed/NCBI
16	Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS and Jones JM: Embryonic stem cell lines derived from human blastocysts. Science. 282:1145–1147. 1998. View Article : Google Scholar : PubMed/NCBI
17	Darr H and Benvenisty N: Genetic analysis of the role of the reprogramming gene LIN-28 in human embryonic stem cells. Stem Cells. 27:352–362. 2009. View Article : Google Scholar
18	Thornton JE, Chang HM, Piskounova E and Gregory RI: Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7). RNA. 18:1875–1885. 2012. View Article : Google Scholar : PubMed/NCBI
19	Mayr F and Heinemann U: Mechanisms of Lin28-mediated miRNA and mRNA regulation - a structural and functional perspective. Int J Mol Sci. 14:16532–16553. 2013. View Article : Google Scholar : PubMed/NCBI
20	Chang TC, Zeitels LR, Hwang HW, et al: Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation. Proc Natl Acad Sci USA. 106:3384–3389. 2009. View Article : Google Scholar : PubMed/NCBI
21	King CE, Cuatrecasas M, Castells A, Sepulveda AR, Lee JS and Rustgi AK: LIN28B promotes colon cancer progression and metastasis. Cancer Res. 71:4260–4268. 2011. View Article : Google Scholar : PubMed/NCBI
22	Xu C, Shen J, Xie S, Jiang Z, Huang L and Wang L: Positive expression of Lin28 is correlated with poor survival in gastric carcinoma. Med Oncol. 30:3822013. View Article : Google Scholar : PubMed/NCBI
23	Teng RY, Zhou JC, Jiang ZN, et al: The relationship between Lin28 and the chemotherapy response of gastric cancer. Onco Targets Ther. 6:1341–1345. 2013. View Article : Google Scholar : PubMed/NCBI