The Roles And Mechanisms Of LncRNA MINCR In Cell Cycle Regulation And Apoptosis In Non-Small Cell Lung Cancer

Objectives: Lung cancer is one of the leading causes of cancer death in the world,and has a relatively low survival rate.Non-small cell lung cancer(NSCLC)is the predominate form which account for 80% of all lung cancer cases.Some effective progresses in chemotherapy and targeted molecular therapies for NSCLC had been made,however certain patients had poor prognosis which attributed to multidrug resistant.Long non-coding RNAs(lnc RNAs)have been demonstrated to modulate cancer progression through a variety of molecular mechanisms.We sought to investigate the role and potential mechanism of MYC-induced long non-coding RNA(MINCR)in NSCLC.Materials and Methods: Expression levels of MINCR was first identified using The Cancer Genome Atlas(TCGA),further confirmed with specimens from NSCLC patients and cell lines using q RT-PCR.Overexpression and knockdown of MINCR were performed in NSCLC cell lines through MINCR overexpression vectors and synthesized si RNAs,respectively.The roles of MINCR in NSCLC cell lines,such as cell proliferation,cell cycle arrest,and apoptosis,were identified by MTT,flow cytometry,and Western blot.The modulation of MINCR-regulated genes,including cMyc and its downstream effectors,as well as apoptosis-associated genes,was analyzed using Western blot.Results: MINCR was aberrantly overexpressed in NSCLC patients,from TCGA atasets,and was also significantly up-regulated in our collected specimens from NSCLC patients and NSCLC cell lines.Knocking down of MINCR greatly inhibited the growth of NSCLC cell lines PC9 and A549.In addition,silencing of MINCR induced cell cycle arrest and apoptosis.Furthermore,silencing of MINCR reduced the expression levels of oncogene c-Myc and its downstream cyclin A,cyclin D,CD4,and CDK2,as well as apoptosis-associated Bcl-2,while significantly increased the expression levels of cleaved PARP-1.In the meantime,overexpression of MINCR remarkably enhanced cell proliferation of PC9 cells and activated c-Myc and its downstream effectors.Conclusion: MINCR exerted inhibitory effects on the cell cycle arrest and apoptosis of NSCLC cells by activating c-Myc and its downstream effectors,suggesting that this lnc RNA could be used as a potential therapeutic target for the treatment of NSCLC.