MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells

被引：145

作者：

Feng, Shipeng ^{[1
,2
,3
]}

Cong, Shujie ^{[1
,2
,3
]}

Zhang, Xin ^{[4
,5
,6
]}

Bao, Xichen ^{[1
,2
,7
]}

Wang, Wei ^{[1
,2
,3
]}

Li, Huiping ^{[1
,2
]}

Wang, Zhe ^{[1
,2
]}

Wang, Guoxin ^{[1
,2
]}

Xu, Jianzhen ^{[1
,2
]}

Du, Bowen ^{[1
,2
,7
]}

Qu, Dezhong ^{[1
,2
,3
]}

Xiong, Wei ^{[1
,2
]}

Yin, Menghui ^{[1
,2
,7
]}

Ren, Xiaoshuai ^{[1
,2
,7
]}

Wang, Feifei ^{[1
,2
]}

He, Jianxing ^{[4
,5
]}

Zhang, Biliang ^{[1
,2
,4
,7
]}

机构：

[1] Chinese Acad Sci, Lab RNA Chem Biol, Guangzhou Inst Biomed, Guangzhou 510530, Guangdong, Peoples R China

[2] Chinese Acad Sci, Lab RNA Chem Biol, Guangzhou Inst Hlth, Guangzhou 510530, Guangdong, Peoples R China

[3] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China

[4] Guangzhou Inst Resp Dis, State Key Lab Resp Dis, Guangzhou 510182, Guangdong, Peoples R China

[5] Guangzhou Med Coll, Affiliated Hosp 1, Dept Cardiothorac Surg, Guangzhou 510182, Guangdong, Peoples R China

[6] Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China

[7] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China

来源：

NUCLEIC ACIDS RESEARCH | 2011年 / 39卷 / 15期

关键词：

P53-INDUCIBLE MICRORNAS; DOWN-REGULATION; MESSENGER-RNAS; EXPRESSION; MIR-192; RB; DIFFERENTIATION; NEPHROPATHY; TRANSCRIPTS; MECHANISM;

D O I：

10.1093/nar/gkr232

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

microRNAs play an important roles in cell growth, differentiation, proliferation and apoptosis. They can function either as tumor suppressors or oncogenes. We found that the overexpression of miR-192 inhibited cell proliferation in A549, H460 and 95D cells, and inhibited tumorigenesis in a nude mouse model. Both caspase-7 and the PARP protein were activated by the overexpression of miR-192, thus suggesting that miR-192 induces cell apoptosis through the caspase pathway. Further studies showed that retinoblastoma 1 (RB1) is a direct target of miR-192. Over-expression of miR-192 decreased RB1 mRNA and protein levels and repressed RB1-3'-UTR reporter activity. Knockdown of RB1 using siRNA resulted in a similar cell morphology as that observed for overexpression of miR-192. Additionally, RB1-siRNA treatment inhibited cell proliferation and induced cell apoptosis in lung cancer cells. Analysis of miRNA expression in clinical samples showed that miR-192 is significantly downregulated in lung cancer tissues compared to adjacent non-cancerous lung tissues. In conclusion, our results demonstrate that miR-192 is a tumor suppressor that can target the RB1 gene to inhibit cell proliferation and induce cell apoptosis in lung cancer cells. Furthermore, miR-192 was expressed at low levels in lung cancer samples, indicating that it might be a promising therapeutic target for lung cancer treatment.

引用

页码：6669 / 6678

页数：10

共 42 条

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