ncRNA basic information
ncRNA ID:
MI0000083/MI0000750
ncRNA Database:
miRBase
ncRNA Name:
miR-26a
ncRNA Type:
miRNA
ncRNA Expression:
up-regulated
ncRNA Method:
RT-qPCR
ncRNA Target Gene:
ULK1
ncRNA Pathway:
NA
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00997 (APRD00185, DB05331, DB05847)
Drug Name:
Doxorubicin
Drug Method:
In the study, we found that chemotherapeutic drug doxorubicin (Dox) induced autophagy but decreased the level of miR-26a/b in HCC cells. Activating autophagy using rapamycin can directly downregulate the level of miR-26a/b in HCC cells. In turn, restoring the expression of miR-26a/b inhibited autophagy induced by Dox and promoted apoptosis in HCC cells. Further mechanistic study identified that miR-26a and miR-26b target ULK1, a critical initiator of autophagy, at post-transcriptional level. Results from 30 cases of patients with HCC also showed that tumor cellular levels of miR-26a and miR-26b are significantly downregulated as compared with the corresponding control tissues and negatively correlated with the protein level of ULK1 but are not correlated to the mRNA level of ULK1. Gain- and loss-of-function assay confirmed that miR-26a/b inhibited autophagic flux at the initial stage through targeting ULK1. Overexpression of miR-26a/b enhanced the sensitivity of HCC cells to Dox and promoted apoptosis via inhibiting autophagy in vitro. Using xenograft models in nude mice, we confirmed that miR-26a/b, via inhibiting autophagy, promoted apoptosis and sensitized hepatomas to Dox treatment in vivo. Our findings demonstrate for the first time that miR-26a/b can promote apoptosis and sensitize HCC to chemotherapy via suppressing the expression of autophagy initiator ULK1, and provide the reduction of miR-26a/b in HCC as a novel mechanism of tumor chemoresistance.
Drug Response:
sensitive
Cancer basic information
Cancer:
hepatocellular carcinoma
Tissue/Cell:
cell line (HepG2, Huh-7, 293T,HepG2/Dox)
Other information
Title:
MiR-26 enhances chemosensitivity and promotes apoptosis of hepatocellular carcinoma cells through inhibiting autophagy.
Journal:
Cell Death Dis
Published:
2017
PubMed ID:
28079894