Int J Biol Sci 2019; 15(8):1664-1675. doi:10.7150/ijbs.35216

Research Paper

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

Jun Weng1*, Xu Han1*, Kaiyu Liu1, Jiong Yang2, Shiruo Wei3, Yue Zhang1, Fanhong Zeng1, Yang Li1, Li Shen3✉, Yi Gao1✉

1. Second Department of Hepatobiliary Surgery, Zhujiang Hospital, State Key Laboratory of Organ Failure Research, Co-Innovation Center for Organ Failure Research, Southern Medical University, Guangzhou, China
2. Department of Geriatrics, The Affiliated Hospital of Qingdao University, Qingdao, China
3. Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
* contributed equally to this work.

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 3ʹ UTR functioned as a ceRNA to regulate the expression of ULBP2 mainly by competing miR-34a. CD44 3ʹ UTR functioned as a ceRNA to enhance NK sensitivity of liver cancer stem cell by regulating ULBP2 expression.

Keywords: liver Cancer Stem Cell • Natural Killer • Post-translational regulation • ceRNA • miR-34a-5p

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How to cite this article:
Weng J, Han X, Liu K, Yang J, Wei S, Zhang Y, Zeng F, Li Y, Shen L, Gao Y. CD44 3'-Untranslated Region Functions as a Competing Endogenous RNA to Enhance NK Sensitivity of Liver Cancer Stem Cell by Regulating ULBP2 Expression. Int J Biol Sci 2019; 15(8):1664-1675. doi:10.7150/ijbs.35216. Available from http://www.ijbs.com/v15p1664.htm