JMJD6-BRD4 Complex Stimulates LncRNA HOTAIR Transcription by Binding to the Promoter Region of HOTAIR and Induces Radioresistance in Liver Cancer Stem Cells

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2023 Oct 26

PMID 37880710

Authors

Ruifeng Pei

Le Zhao

Yiren Ding

Zhan Su

Deqiang Li

Shuo Zhu

Lu Xu

Wei Zhao

Wuyuan Zhou

Affiliations

Soon will be listed here.

Abstract

Background: Long non-coding RNA (lncRNA) HOTAIR acts importantly in liver cancer development, but its effect on radioresistance remains poorly understood. Here, our study probed into the possible impact of HOTAIR in radioresistance in liver cancer stem cells (LCSCs) and to elucidate its molecular basis.

Methods: Following sorting of stem and non-stem liver cancer cells, LCSCs were identified and subjected to RNA-seq analysis for selecting differentially expressed genes. Expression of HOTAIR was determined in liver cancer tissues and CSCs. The stemness, proliferation, apoptosis and radioresistance of LCSCs were then detected in response to altered expression of HOTAIR-LSD1-JMJD6-BRD4.

Results: Ectopic HOTAIR expression was found to promote radioresistance of LCSCs by maintaining its stemness. Mechanistic investigations indicated that HOTAIR recruited LSD1 to the MAPK1 promoter region and reduced the level of H3K9me2 in the promoter region, thus elevating ERK2 (MAPK1) expression. JMJD6-BRD4 complex promoted HOTAIR transcription by forming a complex and positively regulated ERK2 (MAPK1) expression, maintaining the stemness of LCSCs, and ultimately promoting their radioresistance in vitro and in vivo.

Conclusion: Collectively, our work highlights the promoting effect of the JMJD6-BRD4 complex on the radioresistance of LCSCs through a HOTAIR-dependent mechanism.

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