Long non-coding RNA MEG3 induces renal cell carcinoma cells apoptosis by activating the mitochondrial pathway

Miao Wang , Tao Huang , Gang Luo , Chao Huang , Xing-yuan Xiao , Liang Wang , Guo-song Jiang , Fu-qing Zeng

Current Medical Science ›› 2015, Vol. 35 ›› Issue (4) : 541 -545.

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Current Medical Science ›› 2015, Vol. 35 ›› Issue (4) : 541 -545. DOI: 10.1007/s11596-015-1467-5
Article

Long non-coding RNA MEG3 induces renal cell carcinoma cells apoptosis by activating the mitochondrial pathway

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Abstract

This study aimed to examine the effect of long non-coding RNA (LncRNA) MEG3 on the biological behaviors of renal cell carcinoma (RCC) cells 786-0 and the possible mechanism. MEG3 expression levels were detected by RT-qPCR in tumor tissues and adjacent non-tumor tissues from 29 RCC patients and in RCC lines 786-0 and SN12 and human embryonic kidney cell line 293T. Plasmids GV144-MEG3 (MEG3 overexpression plasmid) and GV144 (control plasmid) were stably transfected into 786-0 cells by using lipofectamine 2000. Cell viabilities were determined by MTT, cell apoptosis rates by flow cytometry following PE Annexin V and 7AAD staining, apoptosis-related protein expressions by Western blotting, and Bcl-2 mRNA by RT-qPCR in the transfected cells. The results showed that MEG3 was evidently downregulated in RCC tissues (P<0.05) and RCC cell lines (P<0.05). The viabilities of 786-0 cells were decreased significantly after transfection with GV144-MEG3 for over 24 h (P<0.05). Consistently, the apoptosis rate was significantly increased in 786-0 cells transfected with GV144-MEG3 for 48 h (P<0.05). Furthermore, overexpression of MEG3 could reduce the expression of Bcl-2 and procaspase-9 proteins, enhance the expression of cleaved caspase-9 protein, and promote the release of cytochrome c protein to cytoplasm (P<0.05). Additionally, Bcl-2 mRNA level was declined by MEG3 overexpression (P<0.05). It was concluded that MEG3 induces the apoptosis of RCC cells possibly by activating the mitochondrial pathway.

Keywords

long non-coding RNA (LncRNA) / MEG3 / renal cell carcinoma / apoptosis

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Miao Wang, Tao Huang, Gang Luo, Chao Huang, Xing-yuan Xiao, Liang Wang, Guo-song Jiang, Fu-qing Zeng. Long non-coding RNA MEG3 induces renal cell carcinoma cells apoptosis by activating the mitochondrial pathway. Current Medical Science, 2015, 35(4): 541-545 DOI:10.1007/s11596-015-1467-5

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References

[1]

ReevesDJ, LiuCY. Treatment of metastatic renal cell carcinoma. Cancer Chemother Pharmacol, 2009, 64(1): 11-25 PMID: 19343348

[2]

ChenX, RuanA, WangX, et al. . miR-129-3p, as a diagnostic and prognostic biomarker for renal cell carcinoma, attenuates cell migration and invasion via downregulating multiple metastasis-related genes. J Cancer Res Clin Oncol, 2014, 140(8): 1295-1304 PMID: 24802708

[3]

HockLM, LynchJ, BalajiKC. Increasing incidence of all stages of kidney cancer in the last 2 decades in the United States: an analysis of surveillance, epidemiology and end results program data. J Urol, 2002, 167(1): 57-60 PMID: 11743275

[4]

ChoIC, ChungJ. Current status of targeted therapy for advanced renal cell carcinoma. Korean J Urol, 2012, 53(4): 217-228 PMCID: 3332131 PMID: 22536463

[5]

van BakelH, HughesTR. Establishing legitimacy and function in the new transcriptome. Brief Funct Genomic Proteomic, 2009, 8(6): 424-436 PMID: 19833698

[6]

McPhersonR, PertsemlidisA, KavaslarN, et al. . A common allele on chromosome 9 associated with coronary heart disease. Science, 2007, 316(5830): 1488-1491 PMCID: 2711874 PMID: 17478681

[7]

OkamotoJ, HirataT, ChenZ, et al. . EMX2 is epigenetically silenced and suppresses growth in human lung cancer. Oncogene, 2010, 29(44): 5969-5975 PMCID: 3090446 PMID: 20697358

[8]

ScheuermannJC, BoyerLA. Getting to the heart of the matter: long non-coding RNAs in cardiac development and disease. Embo J, 2013, 32(13): 1805-1816 PMCID: 3981183 PMID: 23756463

[9]

GibbEA, BrownCJ, LamWL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer, 2011, 10: 38 PMCID: 3098824 PMID: 21489289

[10]

YangQQ, DengYF. Long non-coding RNAs as novel biomarkers and therapeutic targets in head and neck cancers. Int J Clin Exp Pathol, 2014, 7(4): 1286-1292 PMCID: 4014209 PMID: 24817925

[11]

FangXY, PanHF, LengRX, et al. . Long noncoding RNAs: novel insights into gastric cancer. Cancer Lett, 2015, 356(2): 357-366 PMID: 25444905

[12]

RonnauCG, VerhaeghGW, Luna-VelezMV, et al. . Noncoding RNAs as novel biomarkers in prostate cancer. Biomed Res Int, 2014, 2014: 591703 PMCID: 4163346 PMID: 25243154

[13]

Schuster-GosslerK, BilinskiP, SadoT, et al. . The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA. Dev Dyn, 1998, 212(2): 214-228 PMID: 9626496

[14]

MiyoshiN, WagatsumaH, WakanaS, et al. . Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells, 2000, 5(3): 211-220 PMID: 10759892

[15]

LiuJ, WanL, LuK, et al. . The long noncoding RNA MEG3 contributes to cisplatin resistance of human lung adenocarcinoma. Plos One, 2015, 10(5): 0114586

[16]

WangP, RenZ, SunP. Overexpression of the long non-coding RNA MEG3 impairs in vitro glioma cell proliferation. J Cell Biochem, 2012, 113(6): 1868-1874 PMID: 22234798

[17]

LuKH, LiW, LiuXH, et al. . Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer, 2013, 13: 461 PMCID: 3851462 PMID: 24098911

[18]

BraconiC, KogureT, ValeriN, et al. . microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene, 2011, 30(47): 4750-4756 PMCID: 4292930 PMID: 21625215

[19]

DebatinKM. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immunother, 2004, 53(3): 153-159 PMID: 14749900

[20]

BlondeauJJ, DengM, SyringI, et al. . Identification of novel long non-coding RNAs in clear cell renal cell carcinoma. Clin Epigenetics, 2015, 7(1): 10 PMCID: 4326488 PMID: 25685243

[21]

QinR, ChenZ, DingY, et al. . Long non-coding RNA MEG3 inhibits the proliferation of cervical carcinoma cells through the induction of cell cycle arrest and apoptosis. Neoplasma, 2013, 60(5): 486-492 PMID: 23790166

[22]

HeY, WuYT, HuangC, et al. . Inhibitory effects of long noncoding RNA MEG3 on hepatic stellate cells activation and liver fibrogenesis. Biochim Biophys Acta, 2014, 1842(11): 2204-2215 PMID: 25201080

[23]

ZhangY, ZouY, WangW, et al. . Down-regulated long non-coding RNA MEG3 and its effect on promoting apoptosis and suppressing migration of trophoblast cells. J Cell Biochem, 2015, 116(4): 542-550 PMID: 25358633

[24]

KawakamiT, ChanoT, MinamiK, et al. . Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma. Hum Mol Genet, 2006, 15(6): 821-830 PMID: 16439445

[25]

ShimizuS, NaritaM, TsujimotoY. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature, 1999, 399(6735): 483-487 PMID: 10365962

[26]

GrossA, McDonnellJM, KorsmeyerSJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev, 1999, 13(15): 1899-1911 PMID: 10444588

[27]

MartinouJC, YouleRJ. Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell, 2011, 21(1): 92-101 PMCID: 3156409 PMID: 21763611

[28]

Budhram-MahadeoV, MorrisPJ, SmithMD, et al. . p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor. J Biol Chem, 1999, 274(21): 15237-15244 PMID: 10329733

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