Characterization of CircSEC11A As a Novel Regulator of Iodine-125 Radioactive Seed-induced Anticancer Effects in Hepatocellular Carcinoma Via Targeting ZHX2/GADD34 Axis

Overview

Journal Cell Death Discov

Date 2023 Aug 10

PMID 37563132

Authors

Dong Li

Wujie Wang

Bin Liu

Die Jin

Yang Wang

Guanghui He

Lei Guo

Wen Liu

Yuliang Li

Affiliations

Soon will be listed here.

Abstract

Iodine-125 (I-125) radioactive seed implantation is used for the local treatment of hepatocellular carcinoma (HCC), but the molecular mechanisms regulating its anticancer effects remain incompletely understood. In this study, we report that hsa_circ_0000647 (circSEC11A) is highly expressed after I-125 treatment in HCC cell lines and tissues and is a key regulator of I-125-induced anticancer effects. CircSEC11A acts as a competing endogenous RNA (ceRNA) to sponge miR-3529-3p, promoting the expression of zinc fingers and homeoboxes 2 (ZHX2) and enhancing I-125-induced anticancer effects. Dual-luciferase reporter assay, RNA pull-down, RNA immunoprecipitation, and fluorescence in situ hybridization were thereafter performed to verify the interaction among the molecules. Anticancer effects were detected using CCK-8, flow cytometry, TUNEL, EdU, transwell, and wound healing assays. Furthermore, ZHX2 transcriptionally inhibits GADD34, a negative regulator of endoplasmic reticulum stress (ERS), to enhance I-125- induced anticancer effects in vivo and in vitro. In conclusion, we characterized circSEC11A as a novel regulator of I-125-induced anticancer effects in HCC via miR-3529-3p/ZHX2/GADD34 axis-mediated ERS. Thus, circSEC11A may act as a potential therapeutic target for I-125 implantation in the clinic.

Citing Articles

Application of radioactive iodine-125 microparticles in hepatocellular carcinoma with portal vein embolus.

Meng P, Ma J, Huang X, Zhang K World J Gastrointest Surg. 2024; 16(7):2023-2030.

PMID: 39087134 PMC: 11287696. DOI: 10.4240/wjgs.v16.i7.2023.

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