miR-15b-5p induces endoplasmic reticulum stress and apoptosis in human hepatocellular carcinoma, both in vitro and in vivo, by suppressing Rab1A

被引:74
作者
Yang, Yang [1 ]
Hou, Ni [1 ]
Wang, Xiaofei [1 ]
Wang, Lumin [1 ]
Chang, Su'e [1 ]
He, Kang [1 ]
Zhao, Zhenghao [1 ]
Zhao, Xiaoge [1 ]
Song, Tusheng [1 ]
Huang, Chen [1 ,2 ,3 ]
机构
[1] Xi An Jiao Tong Univ, Coll Med, Dept Genet & Mol Biol, Xian 710049, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Minist Educ, Key Lab Environm & Genetically Associated Dis, Xian 710049, Shaanxi, Peoples R China
[3] Xi An Jiao Tong Univ, Coll Med, Cardiovasc Res Ctr, Xian 710049, Shaanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-15b-5p; hepatocellular carcinoma; Rab1A; apoptosis; ERS; PROTEIN; PROLIFERATION; HEPATECTOMY; EXPRESSION; DEATH; CELLS;
D O I
10.18632/oncotarget.3970
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:16227 / 16238
页数:12
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