Back to Search
Start Over
Co-targeting of IGF1R/mTOR pathway by miR-497 and miR-99a impairs hepatocellular carcinoma development
- Source :
- Oncotarget
- Publication Year :
- 2017
- Publisher :
- Impact Journals, LLC, 2017.
-
Abstract
- // Henghui Cheng 1, 2 , Jin Xue 1, 2 , Shouhua Yang 3 , Yaobin Chen 1, 2 , Yu Wang 1, 2 , Yuanli Zhu 1, 2 , Xiaoyan Wang 1, 2 , Dong Kuang 1, 2 , Qiurong Ruan 1, 2 , Yaqi Duan 1, 2 and Guoping Wang 1, 2 1 Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China 2 Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China 3 Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China Correspondence to: Yaqi Duan, email: yqduan@hust.edu.cn Guoping Wang, email: wanggp@hotmail.com Keywords: hepatocellular carcinoma, miR-497, miR-99a, IGF1R, mTOR Received: October 24, 2016 Accepted: April 29, 2017 Published: May 24, 2017 ABSTRACT Persistent activation of IGF1R/mTOR signaling pathway plays crucial role in the development of hepatocellular carcinoma (HCC). Therefore, our goal was to elucidate microRNAs (miRNAs) targeting IGF1R/mTOR and the therapeutic potential of single or dual miRNA on HCC development. In this study, we found that miR-497 and miR-99a that target the 3′-UTR of both IGF1R and mTOR were down-regulated in HCC human tissues and cell lines. Functional assay revealed that ectopic expression of miR-497 or miR-99a in HCC cells resulted in a significant inhibition on tumor growth and invasiveness in vitro and tumor development in vivo via repressing the expression of IGF1R and mTOR. Such inhibitory effect on tumor growth is reversed by application of IGF1 ((IGF1R ligand) or MHY1485 (mTOR agonist) in vitro . Furthermore, we found that simultaneous over-expression of both miR-497 and miR-99a exhibited much stronger inhibitory effects on tumor growth than their individual effect, which is still correlated with significantly stronger repression of IGF1R and mTOR. Overall, our results suggest that miR-497 and miR-99a both function as tumor-suppressive miRNAs by suppressing IGF1R/mTOR signaling pathway. The synergistic actions of these two miRNAs partly correlated with IGF1R and mTOR levels, which may represent new strategies for the molecular treatment of HCC.
- Subjects :
- 0301 basic medicine
Carcinoma, Hepatocellular
miR-497
Receptor, IGF Type 1
03 medical and health sciences
0302 clinical medicine
IGF1R
In vivo
Cell Line, Tumor
microRNA
Humans
Medicine
3' Untranslated Regions
Psychological repression
miR-99a
PI3K/AKT/mTOR pathway
Cell Proliferation
Insulin-like growth factor 1 receptor
business.industry
TOR Serine-Threonine Kinases
Cell Cycle
Liver Neoplasms
Receptors, Somatomedin
hepatocellular carcinoma
medicine.disease
body regions
Gene Expression Regulation, Neoplastic
MicroRNAs
Cell Transformation, Neoplastic
030104 developmental biology
Oncology
Cell culture
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Immunology
mTOR
Cancer research
RNA Interference
Ectopic expression
business
Signal Transduction
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....0fd7b5ca427cf40d3d0ad13efa7079b5