2. Academic Validation
  3. The bromodomain inhibitor JQ1 up-regulates the long non-coding RNA MALAT1 in cultured human hepatic carcinoma cells

The bromodomain inhibitor JQ1 up-regulates the long non-coding RNA MALAT1 in cultured human hepatic carcinoma cells

  • Sci Rep. 2022 May 11;12(1):7779. doi: 10.1038/s41598-022-11868-4.
Hae In Choi 1,  Ga Yeong An 1,  Eunyoung Yoo 1,  Mina Baek 2 3,  Bert Binas 2,  Jin Choul Chai 4,  Young Seek Lee 4,  Kyoung Hwa Jung 5,  Young Gyu Chai 6 7
Affiliations

Affiliations

  • 1 Department of Bionanotechnology, Hanyang University, Seoul, 04673, Republic of Korea.
  • 2 Department of Molecular and Life Science, Hanyang University, Ansan, Gyeonggi-do, 15588, Republic of Korea.
  • 3 Institute of Natural Science and Technology, Hanyang University, Ansan, 15588, Republic of Korea.
  • 4 College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.
  • 5 Convergence Technology Campus of Korea Polytechnic II, Incheon, 21417, Republic of Korea. khjung2@gmail.com.
  • 6 Department of Bionanotechnology, Hanyang University, Seoul, 04673, Republic of Korea. ygchai@hanyang.ac.kr.
  • 7 Department of Molecular and Life Science, Hanyang University, Ansan, Gyeonggi-do, 15588, Republic of Korea. ygchai@hanyang.ac.kr.
PMID: 35546353 DOI: 10.1038/s41598-022-11868-4
Abstract

The epigenetic reader, bromodomain-containing 4 (BRD4), is overexpressed in hepatocellular carcinoma (HCC), and BRD4 inhibition is considered as a new therapeutic approach. The Brd Inhibitor JQ1 is known to inhibit the enrichment of BRD4 at enhancer sites. Gene network analyses have implicated long non-coding RNAs (lncRNAs) in the effects of JQ1, but the precise molecular events remain unexplored. Here, we report that in HepG2 cells, JQ1 significantly reduced various proliferation-related lncRNAs, but up-regulated the known liver tumor marker, MALAT1. Using ChIP-sequencing data, ChIP-qPCR, luciferase reporter assays, and chromatin conformation capture (3C), we characterized the MALAT1 gene locus. We found that JQ1 elicited a rearrangement of its chromatin looping conformation, which involved the putative enhancers E1, E2, E3, the gene body, and the promoter. We further found that the forkhead box protein A2 (FOXA2) binds to E2 and the promoter; suppression of FOXA2 expression resulted in MALAT1 up-regulation and increased cell proliferation. These results suggest that the inhibition of MALAT1 may improve the effect of BET inhibitors as an anti-cancer therapy and that FOXA2 would be a suitable target for that approach.

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