miR-15b-5p induces endoplasmic reticulum stress and apoptosis in human hepatocellular carcinoma, both in vitro and in vivo, by suppressing Rab1A
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Yang Yang1, Ni Hou1, Xiaofei Wang1, Lumin Wang1, Su’e Chang1, Kang He1, Zhenghao Zhao1, Xiaoge Zhao1, Tusheng Song1, Chen Huang1,2,3
1Department of Genetics and Molecular Biology, Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi, China
2Key Laboratory of Environmentally and Genetically Associated Diseases at Xi’an Jiaotong University, Ministry of Education, Xi’an, Shaanxi, China
3Cardiovascular Research Center, Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi, China
Chen Huang, e-mail: firstname.lastname@example.org
Tusheng Song, e-mail: email@example.com
Keywords: miR-15b-5p, hepatocellular carcinoma, Rab1A, apoptosis, ERS
Received: February 05, 2015 Accepted: May 06, 2015 Published: May 18, 2015
In human hepatocellular carcinoma (HCC), aberrant expression of miRNAs correlates with tumor cell proliferation, apoptosis, invasion, and migration by targeting downstream proteins. miR-15b levels are reported increased in HCC tissues; however, they negatively correlate to HCC recurrence. Our aim was to understand the reason for this phenomenon. We used the reverse transcription-polymerase chain reaction (RT-PCR) to measure miR-15b-5p expression in both HCC tissues and HCC cell lines. Our results were consistent with the report. Using bioinformatics and luciferase reporter assays, we identified Rab1A as a novel and direct target of miR-15b-5p. Inhibiting the function of Rab1A with shRab1A also inhibited the growth of HCC cells and induced endoplasmic reticulum stress (ERS) and apoptosis. Similarly, suppressing Rab1A by overexpression of miR-15b-5p also inhibited cell growth and induced ERS and apoptosis. Moreover, re-expression of Rab1A rescued the miR-15b-5p-induced ERS, apoptosis, and growth inhibition in HCC cells. In vivo assays were further performed to testify them. Taken together, our data suggest that miR-15b-5p induces ERS, apoptosis, and growth inhibition by targeting and suppressing Rab1A, acting as a tumor suppressor gene in HCC. This finding suggests a novel relation among Rabs, miRNAs, and apoptosis.
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