MIR194-2HG, a miRNA host gene activated by HNF4A, inhibits gastric cancer by regulating microRNA biogenesis.

Autor: Cao H; Department of Orthopaedic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, China., Wang Z; Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, 442000, China., Guo Q; Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, 442000, China., Qin S; Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, 442000, China. qinss77@163.com.; Laboratory of Tumor Biology, Academy of Bio-Medicine Research, Hubei University of Medicine, Shiyan, Hubei, P.R. China. qinss77@163.com.; Shiyan Key Laboratory of Natural Medicine Nanoformulation Research, Hubei University of Medicine, Shiyan, Hubei, 442000, China. qinss77@163.com., Li D; Department of Orthopaedic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, China. lidandan_cup@163.com.; Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, 442000, China. lidandan_cup@163.com.; Laboratory of Tumor Biology, Academy of Bio-Medicine Research, Hubei University of Medicine, Shiyan, Hubei, P.R. China. lidandan_cup@163.com.; Shiyan Key Laboratory of Natural Medicine Nanoformulation Research, Hubei University of Medicine, Shiyan, Hubei, 442000, China. lidandan_cup@163.com.
Jazyk: angličtina
Zdroj: Biology direct [Biol Direct] 2024 Oct 18; Vol. 19 (1), pp. 95. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1186/s13062-024-00549-z
Abstrakt: Background: MicroRNA host gene (MIRHG) lncRNA is a particular lncRNA subclass that can perform both typical and atypical lncRNA functions. The biological function of MIRHG lncRNA MIR194-2HG in cancer is poorly understood.
Methods: Loss-of-function studies were performed in vivo and in vitro to reveal the biological function of MIR194-2HG in GC. MicroRNA PCR array, northern blotting, RNA sequencing, chromatin immunoprecipitation, and rescue assays were conducted to uncover the molecular mechanism of MIR194-2HG.
Results: In this study, we reported an atypical lncRNA function of MIR194-2HG in GC. MIR194-2HG downregulation was clinically associated with malignant progression and poor prognosis in GC. Functional assays confirmed that MIR194-2HG knockdown significantly promoted GC proliferation and metastasis in vitro and in vivo. Mechanismically, MIR194-2HG was required for the biogenesis of miR-194 and miR-192, which were reported to be tumor-suppressor genes in GC. Moreover, hepatocyte nuclear factor HNF4A directly activated the transcription of MIR194-2HG and its derived miR-194 and miR-192. Meanwhile, BTF3L4 was proved to be a common target gene of miR-192 and miR-194. Rescue assay further confirmed that MIR194-2HG knockdown promotes GC progression through maintaining BTF3L4 overexpression in a miR-194/192-dependent manner.
Conclusion: The dysregulated MIR194-2HG/BTF3L4 axis is responsible for GC progression. Targeting HNF4A to inhibit miR-192/194 expression may be a promising strategy for overcoming GC.
(© 2024. The Author(s).)
Databáze: MEDLINE
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