Department of Orthopaedic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, China.
Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, 442000, China.
Biol Direct. 2024 Oct 18;19(1):95. doi: 10.1186/s13062-024-00549-z.
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.
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.
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.
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.
微小 RNA 宿主基因（MIRHG）lncRNA 是一种特殊的 lncRNA 亚类，它可以发挥典型和非典型 lncRNA 的功能。MIRHG lncRNA MIR194-2HG 在癌症中的生物学功能知之甚少。
在体内和体外进行功能丧失研究，以揭示 MIR194-2HG 在 GC 中的生物学功能。进行 microRNA PCR 阵列、 northern 印迹、RNA 测序、染色质免疫沉淀和挽救实验，以揭示 MIR194-2HG 的分子机制。
在本研究中，我们报道了 MIR194-2HG 在 GC 中的一种非典型 lncRNA 功能。MIR194-2HG 的下调与 GC 的恶性进展和预后不良相关。功能测定证实，MIR194-2HG 敲低显著促进 GC 体外和体内的增殖和转移。机制上，MIR194-2HG 是 miR-194 和 miR-192 生物发生所必需的，据报道，miR-194 和 miR-192 是 GC 中的肿瘤抑制基因。此外，肝细胞核因子 HNF4A 直接激活 MIR194-2HG 及其衍生的 miR-194 和 miR-192 的转录。同时，BTF3L4 被证明是 miR-192 和 miR-194 的共同靶基因。挽救实验进一步证实，MIR194-2HG 敲低通过维持 miR-194/192 依赖性的 BTF3L4 过表达促进 GC 进展。
失调的 MIR194-2HG/BTF3L4 轴负责 GC 的进展。靶向 HNF4A 抑制 miR-192/194 的表达可能是克服 GC 的一种有前途的策略。
