Identification and functional characterization of two noncoding rnas transcribed from putative active enhancers in hepatocellular carcinoma

Ye Eun Lee, Jiyeon Lee, Yong Sun Lee, Jiyoung Joan Jang, Hyeonju Woo, Hae In Choi, Young Gyu Chai, Tae Kyung Kim, Taesoo Kim, Lark Kyun Kim, Sun Shim Choi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Enhancers have been conventionally perceived as cis-acting elements that provide binding sites for trans-acting factors. However, recent studies have shown that enhancers are transcribed and that these transcripts, called enhancer RNAs (eRNAs), have a regulatory function. Here, we identified putative eRNAs by profiling and determining the overlap between noncodi ng RNA expressi on l oci and eRNA-associated histone marks such as H3K27ac and H3K4me1 in hepatocellular carcinoma (HCC) cell lines. Of the 132 HCC-derived noncoding RNAs, 74 overlapped with the eRNA loci defined by the FANTOM consortium, and 65 were located in the proximal regions of genes differentially expressed between normal and tumor tissues in TCGA dataset. Interestingly, knockdown of two selected putative eRNAs, THUMPD3-AS1 and LINC01572, led to downregulation of their target mRNAs and to a reduction in the proliferation and migration of HCC cells. Additionally, the expression of these two noncoding RNAs and target mRNAs was elevated in tumor samples in the TCGA dataset, and high expression was associated with poor survival of patients. Collectively, our study suggests that noncoding RNAs such as THUMPD3-AS1 and LINC01572 (i.e., putative eRNAs) can promote the transcription of genes involved in cell proliferation and differentiation and that the dysregulation of these noncoding RNAs can cause cancers such as HCC.

Original languageEnglish (US)
Pages (from-to)658-669
Number of pages12
JournalMolecules and Cells
Volume44
Issue number9
DOIs
StatePublished - Sep 2021
Externally publishedYes

Keywords

  • Enhancer RNA
  • Hepatocellular carcinoma
  • Long noncoding RNA
  • RNA polymerase II
  • Transcribed enhancer
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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