The long noncoding RNA GAS8-AS1 suppresses hepatocarcinogenesis by epigenetically activating the tumor suppressor GAS8

The Journal of Biological Chemistry
Wenting PanMing Yang

Abstract

Long noncoding RNAs (lncRNAs) are vital players in cancers, including hepatocellular carcinoma (HCC). We previously identified an lncRNA, GAS8-AS1, that is located in intron 2 of GAS8 However, its involvement in HCC is still largely unknown. In this study, we report that both GAS8-AS1 and its host gene GAS8 act as HCC tumor suppressors. We found that expression of GAS8-AS1 or GAS8 is significantly decreased in HCC tissues and is associated with a poor prognosis among HCC patients. Interestingly, lncRNA GAS8-AS1 could promote GAS8 transcription. We detected a CpG island in the GAS8 promoter, but lncRNA GAS8-AS1 did not affect DNA methylation at this GAS8 promoter site. Moreover, we identified two GAS8-AS1-interacting proteins, mixed-lineage leukemia 1 (MLL1), a histone 3 Lys-4 (H3K4) methyltransferase, and its partner WD-40 repeat protein 5 (WDR5). RNA pulldown, ChIP, and RNA immunoprecipitation assays revealed that GAS8-AS1 is required for maintaining the GAS8 promoter in an open chromatin state by recruiting the MLL1/WDR5 complex and for enhancing RNA polymerase II activity and GAS8 transcription. Of note, GAS8-AS1-dependent GAS8 hyperactivation inhibited malignant transformation of hepatocytes. Our results provide important i...Continue Reading

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Citations

Jul 18, 2020·Cancer Biomarkers : Section a of Disease Markers·Da-Lei ZhouCai-Yun He
Aug 31, 2019·Cancers·Saranya Chidambaranathan Reghupaty, Devanand Sarkar
Mar 14, 2020·Experimental and Molecular Pathology·Sepideh DashtiMohammad Taheri
Jan 1, 2020·RNA Biology·Yan HuangXiangting Wang
Dec 11, 2020·BioMed Research International·Mohamed H YousefAnwar Abdelnaser
Jan 29, 2021·World Journal of Gastroenterology : WJG·Guang-Lin LeiPeng-Hui Yang
Apr 11, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ganglei LiJian Shen
May 4, 2021·Frontiers in Cell and Developmental Biology·Jixing ZhangHe Zhang
May 11, 2021·Frontiers in Oncology·Soudeh Ghafouri-FardMohammad Taheri
Aug 16, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Ganesh Kumar BarikBhargab Kalita
Oct 8, 2021·The Journal of International Medical Research·Junhua LuoYan Wang
Nov 2, 2021·International Journal of Cancer. Journal International Du Cancer·Andrew R MarleyXin Li

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