论文简介 |
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 identifed 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 fnding suggests a novel relation among Rabs,
miRNAs, and apoptosis. |