Targeting of non-coding RNAs encoded by novel MYC enhancers inhibits the proliferation of human hepatic carcinoma cells in vitro

Abstract The proto-oncogene MYC is important for development and cell growth, however, its abnormal regulation causes cancer. Recent studies identified distinct enhancers of MYC in various cancers, but any MYC enhancer(s) in hepatocellular carcinoma (HCC) remain(s) elusive. By analyzing H3K27ac enri...

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Bibliographic Details
Published inScientific reports Vol. 12; no. 1
Main Authors Choi, Hae In, An, Ga Yeong, Yoo, Eunyoung, Baek, Mina, Chai, Jin Choul, Binas, Bert, Lee, Young Seek, Jung, Kyoung Hwa, Chai, Young Gyu
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 17.01.2022
Nature Publishing Group UK
Subjects
Antisense oligonucleotides
Cell growth
Cell proliferation
CRISPR
Enhancers
Gene deletion
Hepatocellular carcinoma
Liver cancer
Myc protein
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Summary:Abstract The proto-oncogene MYC is important for development and cell growth, however, its abnormal regulation causes cancer. Recent studies identified distinct enhancers of MYC in various cancers, but any MYC enhancer(s) in hepatocellular carcinoma (HCC) remain(s) elusive. By analyzing H3K27ac enrichment and enhancer RNA (eRNA) expression in cultured HCC cells, we identified six putative MYC enhancer regions. Amongst these, two highly active enhancers, located ~ 800 kb downstream of the MYC gene, were identified by qRT-PCR and reporter assays. We functionally confirmed these enhancers by demonstrating a significantly reduced MYC expression and cell proliferation upon CRISPR/Cas9-based deletion and/or antisense oligonucleotide (ASO)-mediated inhibition. In conclusion, we identified potential MYC enhancers of HCC and propose that the associated eRNAs may be suitable targets for HCC treatment.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-04869-w