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Identification and Functional Characterization of Two Noncoding RNAs Transcribed from Putative Active Enhancers in
Ye-Eun Lee1,2, Jiyeon Lee3,2, Yong Sun Lee4
1Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Korea.
Molecules and Cells
|September 30, 2021
Summary
Novel enhancer RNAs (eRNAs) like THUMPD3-AS1 and LINC01572 regulate hepatocellular carcinoma (HCC) cell growth. Their elevated expression in tumors correlates with poor patient survival, suggesting a role in cancer development.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- Traditionally, enhancers were considered static DNA regions binding regulatory proteins.
- Emerging evidence reveals enhancers are transcribed into enhancer RNAs (eRNAs) with regulatory roles.
- The function of eRNAs in hepatocellular carcinoma (HCC) remains largely unexplored.
Purpose of the Study:
- To identify and characterize novel enhancer RNAs (eRNAs) in hepatocellular carcinoma (HCC).
- To investigate the functional role of putative eRNAs in HCC cell proliferation and migration.
- To assess the clinical significance of identified eRNAs in HCC patient survival.
Main Methods:
- Profiling noncoding RNA expression and identifying overlap with enhancer-associated histone marks (H3K27ac, H3K4me1) in HCC cell lines.
- Analyzing overlap with FANTOM consortium eRNA loci and proximity to differentially expressed genes in The Cancer Genome Atlas (TCGA) dataset.
- Performing knockdown experiments for candidate eRNAs (THUMPD3-AS1, LINC01572) and assessing effects on target mRNAs and HCC cell behavior.
Main Results:
- Identified 132 HCC-derived noncoding RNAs, with 74 overlapping eRNA loci and 65 near differentially expressed genes.
- Knockdown of THUMPD3-AS1 and LINC01572 reduced HCC cell proliferation and migration, downregulating target mRNAs.
- THUMPD3-AS1 and LINC01572 expression, along with their target mRNAs, were elevated in HCC tumors, correlating with poor patient survival.
Conclusions:
- Noncoding RNAs, specifically THUMPD3-AS1 and LINC01572 (putative eRNAs), promote HCC cell proliferation and differentiation.
- Dysregulation of these eRNAs contributes to the development of hepatocellular carcinoma.
- These eRNAs represent potential diagnostic biomarkers and therapeutic targets for HCC.
Keywords:
RNA polymerase IIenhancer RNAhepatocellular carcinomalong noncoding RNAtranscribed enhancertranscriptional regulationMore Related Videos
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