Identification and Functional Characterization of Two Noncoding RNAs Transcribed from Putative Active Enhancers in Hepatocellular Carcinoma
- 주제(키워드) enhancer RNA ,   , hepatocellular carcinoma ,   , long noncoding RNA ,   , RNA polymerase II ,   , transcribed enhancer ,   , transcriptional regulation
- 주제(기타) Biochemistry & Molecular Biology; Cell Biology
- 설명문(일반) [Lee, Ye-Eun; Choi, Sun Shim] Kangwon Natl Univ, Inst Biosci & Biotechnol, Coll Biomed Sci, Div Biomed Convergence, Chunchon 24341, South Korea; [Lee, Jiyeon; Kim, Lark Kyun] Yonsei Univ, Gangnam Severance Hosp, Severance Biomed Sci Inst, Grad Sch Med Sci,Brain Korea Project 21,Coll Med, Seoul 06230, South Korea; [Lee, Yong Sun; Jang, Jiyoung Joan] Natl Canc Ctr, Grad Sch Canc Sci & Policy, Dept Canc Biomed Sci, Goyang 10408, South Korea; [Woo, Hyeonju; Kim, TaeSoo] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Woo, Hyeonju; Kim, TaeSoo] Ewha Womans Univ, Res Ctr Cellular Homeostasis, Seoul 03760, South Korea; [Choi, Hae In] Hanyang Univ, Dept Bionanotechnol, Seoul 04673, South Korea; [Chai, Young Gyu] Hanyang Univ, Dept Mol & Life Sci, Ansan 15588, South Korea; [Kim, Tae-Kyung] Pohang Univ Sci & Technol POSTECH, Dept Life Sci, Pohang 37673, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- OA유형 Green Published, gold
- 발행기관 KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183657
- 본문언어 영어
- Published As http://dx.doi.org/10.14348/molcells.2021.0173
- PubMed https://pubmed.ncbi.nlm.nih.gov/34588321
초록/요약
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 noncoding RNA expression loci and eRNAassociated histone marks such as H3K27ac and H3K4me1 in hepatocellular carcinoma (HCC) cell lines. Of the 132 HCCderived 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 THUMPD3AS1 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.
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