MiR-511 inhibits growth and metastasis of human hepatocellular carcinoma cells by targeting PIK3R3

被引:39
作者
Cao, Gang [1 ,2 ]
Dong, Weihua [1 ]
Meng, Xiaoxi [1 ]
Liu, Hongchao [1 ]
Liao, Huaqiang [1 ]
Liu, Shiyuan [1 ]
机构
[1] Second Mil Med Univ, Dept Radiol & Nucl Med, Shanghai Changzheng Hosp, Shanghai 200003, Peoples R China
[2] First Peoples Hosp Lian Yungang, Dept Intervent Radiol, Lian Yungang 222002, Jiangsu, Peoples R China
关键词
miR-511; Hepatocellular carcinoma; PIK3R3; Proliferation; Invasion; MICRORNA; PROMOTES; CANCER; EXPRESSION; PHOSPHOINOSITIDE-3-KINASE; PROLIFERATION; BIOGENESIS;
D O I
10.1007/s13277-015-3085-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs (miRNAs) are critical for cancer development and progression. Elucidating the underlying mechanism of miRNAs in carcinogenesis may lead to novel diagnostic and therapeutic strategies for malignancy. In this study, we found that miR-511 expression was markedly downregulated in hepatocellular carcinoma (HCC) cell lines and tissues. Phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was identified as a direct target of miR-511 and miR-511 expression inversely correlated with PIK3R3 mRNA expression in clinical HCC tissues. We further demonstrated that miR-511 suppressed HCC cell proliferation, migration, and invasion by repressing PIK3R3 expression. Investigations of possible mechanisms underlying these results revealed that miR-511 inhibited the phosphorylation of AKT and mTOR, which are key participants in the AKT/mTOR pathway. Taken together, our findings provide new insights into tumor suppression by miR-511 by negatively regulating the PIK3R3/AKT/mTOR signaling pathway.
引用
收藏
页码:4453 / 4459
页数:7
相关论文
共 31 条
[1]   MicroRNA as potential biomarker in HCV-associated diffuse large B-cell lymphoma [J].
Augello, Claudia ;
Gianelli, Umberto ;
Savi, Federica ;
Moro, Alessia ;
Bonoldi, Emanuela ;
Gambacorta, Marcello ;
Vaira, Valentina ;
Baldini, Luca ;
Bosari, Silvano .
JOURNAL OF CLINICAL PATHOLOGY, 2014, 67 (08) :697-701
[2]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]   MicroRNA-331-3p Promotes Proliferation and Metastasis of Hepatocellular Carcinoma by Targeting PH Domain and Leucine-Rich Repeat Protein Phosphatase [J].
Chang, Rui-Min ;
Yang, Hao ;
Fang, Feng ;
Xu, Jiang-Feng ;
Yang, Lian-Yue .
HEPATOLOGY, 2014, 60 (04) :1251-1263
[4]   MicroRNA-100 promotes the autophagy of hepatocellular carcinoma cells by inhibiting the expression of mTOR and IGF-1R [J].
Ge, Yi-Yuan ;
Shi, Qing ;
Zheng, Zhi-Yuan ;
Gong, Jiao ;
Zeng, Chunxian ;
Yang, Jine ;
Zhuang, Shi-Mei .
ONCOTARGET, 2014, 5 (15) :6218-6228
[5]  
JEMAL A, 2011, CA-CANCER J CLIN, V61, P69, DOI DOI 10.3322/CAAC.20107
[6]   Deregulation of miR-519a, 153, and 485-5p and its clinicopathological relevance in ovarian epithelial tumours [J].
Kim, Tae Heon ;
Kim, Yu Kyung ;
Kwon, Youngdo ;
Heo, Jin Hyung ;
Kang, Haeyoun ;
Kim, Gwangil ;
An, Hee Jung .
HISTOPATHOLOGY, 2010, 57 (05) :734-743
[7]   Biogenesis of small RNAs in animals [J].
Kim, V. Narry ;
Han, Jinju ;
Siomi, Mikiko C. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (02) :126-139
[8]   Computational Analysis of mRNA Expression Profiles Identifies the ITG Family and PIK3R3 as Crucial Genes for Regulating Triple Negative Breast Cancer Cell Migration [J].
Klahan, Sukhontip ;
Wu, Mei-Shin ;
Hsi, Edward ;
Huang, Chi-Cheng ;
Hou, Ming-Feng ;
Chang, Wei-Chiao .
BIOMED RESEARCH INTERNATIONAL, 2014, 2014
[9]   Hepatitis B virus X protein promotes hepatocellular carcinoma transformation through interleukin-6 activation of microRNA-21 expression [J].
Li, Chi Han ;
Xu, Feiyue ;
Chow, Sheungching ;
Feng, Lu ;
Yin, Deling ;
Ng, Tzi Bun ;
Chen, Yangchao .
EUROPEAN JOURNAL OF CANCER, 2014, 50 (15) :2560-2569
[10]  
Li L, 2014, HEPATOLOGY