CD44 3'-Untranslated Region Functions as a Competing Endogenous RNA to Enhance NK Sensitivity of Liver Cancer Stem Cell by Regulating ULBP2 Expression

International Journal of Biological Sciences
Jun WengYi Gao

Abstract

Liver CSCs are a rare subpopulation of heterogenous liver cancer cells with self-renewal and differentiation properties, which has emerged as a promising therapeutic target. Compelling data shows that NK cells selectively eliminate human cancer derived CSCs like colorectal carcinoma, melanoma, and glioblastoma. But the effect of NK cells on liver CSCs still remains unknown. To study the cytotoxic effect of NK cells on liver CSCs and the mechanism, we performed cytotoxicity assay, ELISA assays, CRISPRi, qRT-PCR, immunoblotting, RNA immunoprecipitation, and luciferase reporter using two types of CSCs reprogrammed from HCC. CSCs derived from liver cancer were susceptible to NK cell mediated cytotoxicity. The susceptibility of liver CSCs to NK cell-mediated cytotoxicity declined significantly after silencing CD44 by CRISPRi-mediated gene knockdown. CD44 3' UTR functioned as a ceRNA to regulate the expression of ULBP2 mainly by competing miR-34a. CD44 3' UTR functioned as a ceRNA to enhance NK sensitivity of liver cancer stem cell by regulating ULBP2 expression.

Citations

Jul 17, 2020·OncoTargets and Therapy·Yi Fan LiWen Bin Wei
Dec 12, 2020·Experimental Hematology & Oncology·Hanxiao XuAiguo Liu
Mar 26, 2021·Frontiers in Cell and Developmental Biology·Wen Jess LiDean G Tang

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Methods Mentioned

BETA
Assay
ELISA
PCR
immunoprecipitations
immunoprecipitation
RIP
transfection
fluorescence activated cell sorting

Software Mentioned

StarBase
GraphPad
ceRNA
ImageJ
Prism

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