Inhibition of cell proliferation and induction of autophagy by KDM2B/FBXL10 knockdown in gastric cancer cells

Cellular Signalling
Erhu ZhaoHongjuan Cui

Abstract

Gastric cancer is difficult to cure due to its clinical heterogeneity and the complexity of its molecular mechanisms. KDM2B, a member of the JHDM family, functions as a histone lysine demethylase. However, the role and mechanisms of KDM2B in gastric cancer have not been elucidated. Here, we showed that KDM2B is commonly expressed in gastric cancer cells. The downregulation of KDM2B immediately induces autophagy, followed by the inhibition of proliferation. The compound 3-methyladenine (3-MA), an inhibitor of autophagy, largely rescues autophagy and the inhibition of cell proliferation induced by KDM2B knockdown. In this process, we observed a downregulation of the phosphorylation of Akt and its downstream effectors mTOR and p70S6K and an upregulation of Erk phosphorylation after KDM2B knockdown. In a xenograft model, the downregulation of KDM2B can inhibit tumour growth. The conversion of LC3-I to LC3-II also decreased concomitantly in vivo, which is a hallmark of autophagy. Taken together, our study was the first to demonstrate a novel regulatory role of KDM2B in autophagy and cell growth in gastric cancer cells. Our findings suggest that KDM2B may serve as a novel therapeutic target for gastric cancer therapy.

Citations

Feb 1, 2019·Journal of Cellular and Molecular Medicine·Leilei YinXinhua Yin
Feb 14, 2019·Expert Opinion on Therapeutic Targets·Tyler S McCannPaul Jedlicka
Mar 17, 2020·Cancer Biology & Therapy·Nefeli ZacharopoulouChristos Stournaras
May 17, 2019·Indian Journal of Clinical Biochemistry : IJCB·Aman KumarRajendra Prasad
Sep 19, 2019·Journal of Cellular Physiology·Yuxi Qi, Yanning Zhao
Sep 19, 2018·BMC Genomics·Maria BallesterRaquel Quintanilla
Sep 23, 2020·Journal of Experimental & Clinical Cancer Research : CR·Erhu ZhaoHongjuan Cui
Sep 24, 2019·Cancer Letters·Min LinZhi-Wei Wang
Oct 5, 2020·Life Sciences·Sadegh FattahiHaleh Akhavan-Niaki
Dec 27, 2019·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Linzhi YanXueqiong Zhu
Apr 2, 2021·Frontiers in Oncology·Jaceline Gisliane Pires SanchesLianhong Li
Apr 14, 2021·Nature Chemical Biology·Ryan J WeissJeffrey D Esko
Apr 30, 2021·Frontiers in Cell and Developmental Biology·Longchang BaiHongjuan Cui
Jul 13, 2021·World Journal of Stem Cells·Harpreet K MandhairRamin Radpour
Jul 6, 2021·Frontiers in Genetics·Gaya Punnia-MoorthyJessamy Tiffen

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