LncRNA Miat Promotes Proliferation of Cervical Cancer Cells and Acts as an Anti-apoptotic Factor

Document Type : Research Article

Authors

Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran

Abstract

There are a sub-population of cells in tumor tissues known as cancer stem cells (CSCs) which have similar features with stem cells, including self-renewal and differentiation capacity. Recently, it was established that not only stem cells factors such as Oct4, but also ES-associated lncRNAs are contributing to various regulatory aspects of CSCs. Myocardial infarction associated transcript (MIAT) is a lncRNA which expressed in embryonic stem cells (ESCs) and its expression was regulated by ES-associated transcription factors, Oct4 and Nanog. Here, our results revealed that suppression of MIAT reduces cell proliferation and causes G1 arrest in HeLa cancer cells through downregulation of cell cycle progression factors including, CyclinD1 and PCNA. Furthermore, our data showed that downregulation of MIAT represses migration of HeLa cells which implicated that MIAT may be contributed to the migration of HeLa cells. We further detected MIAT silencing promotes apoptosis of Hela cancer cells and influences the expression of known apoptotic factors, Bcl2 and Bax. Based on our findings, LncRNA MIAT might be involved in the cervical cancer malignant progression and it could be the candidate as a potential therapeutic target to combat cancer.

Keywords


Asadi MH, Mowla SJ, Fathi F, Aleyasin A, Asadzadeh J, Atlasi Y. 2011. OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor. Int J Cancer 128:2645-2652.
Atkinson SR, Marguerat S, Bähler J. 2012. Exploring long non-coding RNAs through sequencing. Sem Cell Develop Biol 23(2): 200-205.
Kashi K, Henderson L, Bonetti A, Carninci P. 2016. Discovery and functional analysis of lncRNAs: Methodologies to investigate an uncharacterized transcriptome. Biochim Biophys Acta 1859(1):3-15.
Lai IL, Yang CA, Lin PC, Chan WL, Lee YT, Yen JC, Chang YS, Chang JG. 2017. Long noncoding RNA MIAT promotes non-small cell lung cancer proliferation and metastasis through MMP9 activation. Oncotarget 8:98148.
Lalevée S, Feil R. 2015. Long noncoding RNAs in human disease: emerging mechanisms and therapeutic strategies. Future Med 7:877-879.
Li D, Ainiwaer J, Sheyhiding I, Zhang Z, Zhang L. 2016. Identification of key long non-coding RNAs as competing endogenous RNAs for miRNA-mRNA in lung adenocarcinoma. Eur Rev Med Pharmacol Sci 20:2285-2295.
Maugeri-Saccà M, Vici P, Di Lauro L, Barba M, Amoreo CA, Gallo E, Mottolese M, De Maria R. 2014. Cancer stem cells: are they responsible for treatment failure? Future Oncol 10:2033-2044.
Mercer TR, Dinger ME, Mattick JS. 2009. Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155-159.
Mohamed JS, Gaughwin PM, Lim B, Robson P, Lipovich L. 2010. Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA 16:324-337.
Qu X, Du Y, Shu Y, Gao M, Sun F, Luo S, Yang T, Zhan L, Yuan Y, Chu W. 2017. MIAT is a pro-fibrotic long non-coding RNA governing cardiac fibrosis in post-infarct myocardium. Sci Rep 7:42657.
Rao S-Q, Hu H-L, Ye N, Shen Y, Xu Q. 2015. Genetic variants in long non-coding RNA MIAT contribute to risk of paranoid schizophrenia in a Chinese Han population. Schizophrenia Res 166:125-130.
Rinn JL, Chang HY. 2012. Genome regulation by long noncoding RNAs. Annu Rev Bibiochem 81:145-166.
Sheik Mohamed J, Gaughwin PM, Lim B, Robson P, Lipovich L. 2010. Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA 16:324-37.
Tafrihi M, Toosi S, Minaei T, Gohari AR, Niknam V, Arab  Najafi SM. 2014. Anticancer properties of Teucrium persicum in PC-3 prostate cancer cells. Asia Pac J Cancer Prevent 15(2): 785-791.
Vinogradov S, Wei X. 2012. Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine 7:597-615.
Zhang HY, Zheng FS, Yang W, Lu JB. 2017. The long non-coding RNA MIAT regulates zinc finger E-box binding homeobox 1 expression by sponging miR-150 and promoteing cell invasion in non-small-cell lung cancer. Gene 633:61-65.