KCNQ1OT1 contributes to sorafenib resistance and programmed deathligand1mediated immune escape via sponging miR506 in hepatocellular carcinoma cells.
Int J Mol Med
; 46(5): 1794-1804, 2020 Nov.
Article
in En
| MEDLINE
| ID: mdl-33000204
ABSTRACT
Drug resistance and immune escape of tumor cells severely compromise the treatment efficiency of hepatocellular carcinoma (HCC). Long noncoding RNA KCNQ1 overlapping transcript 1 (lncRNA KCNQ1OT1) has been shown to be involved in drug resistance in several cancers. The aim of the present study was to investigate the role of KCNQ1OT1 in sorafenib resistance and immune escape of HCC cells. Reverse transcriptionquantitative PCR analysis, western blotting and immunohistochemistry were performed to detect the expression of KCNQ1OT1, miR506 and programmed deathligand1 (PDL1). Cell Counting Kit8 assay, flow cytometry and Transwell assays were used to evaluate IC50 value, cell apoptosis and metastasis. ELISA was performed to detect the secretion of cytokines. Dualluciferase reporter assay was conducted to verify the targeting relationships between miR506 and KCNQ1OT1 or PDL1. KCNQ1OT1 and PDL1 were found to be upregulated and miR506 was downregulated in sorafenibresistant HCC tissues and cells. Furthermore, KCNQ1OT1 knockdown reduced the IC50 value of sorafenib, suppressed cell metastasis and promoted apoptosis in sorafenibresistant HCC cells. Moreover, KCNQ1OT1 knockdown changed the tumor microenvironment and Tcell apoptosis in a sorafenibresistant HCC/Tcell coculture model. In addition, it was demonstrated that KCNQ1OT1 functioned as a competing endogenous RNA of miR506 and increased PDL1 expression in sorafenibresistant HCC cells. miR506 inhibition abolished the effects of KCNQ1OT1 knockdown on sorafenib sensitivity, tumor growth, the tumor microenvironment and Tcell apoptosis. In conclusion, KCNQ1OT1 knockdown inhibited sorafenib resistance and PDL1mediated immune escape by sponging miR506 in sorafenibresistant HCC cells.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Hepatocellular
/
Drug Resistance, Neoplasm
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MicroRNAs
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Immune Evasion
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B7-H1 Antigen
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Sorafenib
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Liver Neoplasms
Limits:
Humans
Language:
En
Journal:
Int J Mol Med
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2020
Document type:
Article