Published online Dec 28, 2021. doi: 10.3748/wjg.v27.i48.8302
Peer-review started: April 27, 2021
First decision: June 13, 2021
Revised: June 22, 2021
Accepted: November 11, 2021
Article in press: December 11, 2021
Published online: December 28, 2021
Hepatocellular carcinoma (HCC) is a frequently diagnosed malignant tumor caused by its main risk factor, hepatitis B virus (HBV) infection. HBV infection alters the level of miRNA in cells, which can be delivered to surrounding cells by exosomes to affect disease progression.
HCC is a common malignant tumor with relatively insipid early symptoms, rapid disease progression, burdensome treatment, and poor prognosis. Since HBV infection is still one of the major causes of HCC in China, the mechanism of HBV in HCC resistance remains unclear.
To explore the role of hepatitis B core antigen (HBc) on Dox-induced HCC resistance and the underlying mechanism.
Exosomes were isolated by ultracentrifugation. The miRNAs differentially expressed in HCC were identified using the Cancer Genome Atlas (TCGA) database. The level of miR-135a-5p in patient tissues and exosomes was detected by quantitative polymerase chain reaction. After transfection with the indicated plasmids, cell functions affected by the HBV-regulated miR-135a/vesicle-associated membrane protein 2 (VAMP2) axis were assessed by flow cytometry and cell counting kit 8 assay.
miR-135a-5p expression was upregulated in HCC tissues and cells. HBc increased the expression of exosomal miR-135a-5p. VAMP2 is one of the potential target genes of miR-135a-5p, and functional assays showed that HBc mediated the miR-135a/VAMP2 axis to induce apoptosis protection, cell proliferation, and chemotherapy resistance in HCC.
HBc elevated the expression of exosomal miR-135a-5p and promoted anti-apoptosis, cell proliferation, and chemical resistance through miR-135a-5p/VAMP2 in HCC.
The role of the miR-135a-5p/VAMP2 regulatory axis in chemotherapy resistance of HCC may serve as a potential molecular therapeutic target for HCC.