Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Hefei, P. R. China.
College of Basic Medical Sciences, Dalian Medical University, Dalian, P. R. China.
Bioengineered. 2022 Apr;13(4):8370-8381. doi: 10.1080/21655979.2022.2026858.
Long non-coding RNAs (lncRNAs) have been widely recognized as critical players in the development of nonalcoholic fatty liver disease (NAFLD), one of the most prevalent liver diseases globally. In this study, we established a HFD-induced NAFLD mouse model and explored the role of lncRNA GAS5 in NAFLD progression and its possible underlying mechanisms. We showed that NAFLD activity score was elevated in the HFD mice. GAS5 knockdown attenuated HFD-induced hepatic steatosis and lipid accumulation and reduced NAFLD activity score in HFD mice. In addition, GAS5 knockdown reduced serum triglyceride cholesterol levels and inhibited alanine aminotransferase and aspartate aminotransferase activities in HFD mice. Moreover, GAS5 overexpression enhanced NOTCH2 levels in liver cells and promoted NAFLD progression by sponging miR-29a-3p . Furthermore, miR-29a-3p inhibited NAFLD progression by targeting NOTCH2 . Overall, our results indicated that GAS5 acts as a sponge of miR-29a-3p to increase NOTCH2 expression and facilitate NAFLD progression by targeting the miR-29a-3p/NOTCH2 axis and demonstrated a new GAS5-mediated mechanism underlying NAFLD development, suggesting that GAS5 could be a potential therapeutic target of NAFLD. Alanine aminotransferase: ALT; Aspartate aminotransferase: AST; Enzyme linked immunosorbent assay: ELISA; Hepatocellular carcinoma: HCC; High-fat diet: HFD; Long non-coding RNA: Lnc RNA; Long non-coding RNA GAS5: GAS5; MicroRNAs: MiRNAs; Nonalcoholic fatty liver disease: NAFLD; Quantitative reverse transcription PCRs: RT-qPCRs; siRNA negative control: si-NC; Total cholesterol: TC; Triglyceride: TG.
长链非编码 RNA（lncRNA）已被广泛认为是非酒精性脂肪性肝病（NAFLD）发展的关键因素之一，NAFLD 是全球最常见的肝脏疾病之一。在本研究中，我们建立了高脂肪饮食（HFD）诱导的 NAFLD 小鼠模型，探讨了 lncRNA GAS5 在 NAFLD 进展中的作用及其可能的潜在机制。结果表明，HFD 小鼠的 NAFLD 活性评分升高。GAS5 敲低可减轻 HFD 诱导的肝脂肪变性和脂质堆积，并降低 HFD 小鼠的 NAFLD 活性评分。此外，GAS5 敲低可降低血清甘油三酯和胆固醇水平，并抑制 HFD 小鼠中丙氨酸氨基转移酶和天冬氨酸氨基转移酶的活性。此外，GAS5 过表达可增加肝细胞中的 NOTCH2 水平，并通过海绵吸附 miR-29a-3p 促进 NAFLD 进展。此外，miR-29a-3p 通过靶向 NOTCH2 抑制 NAFLD 进展。综上所述，我们的研究结果表明，GAS5 通过作为 miR-29a-3p 的海绵吸附物增加 NOTCH2 表达，并通过靶向 miR-29a-3p/NOTCH2 轴促进 NAFLD 进展，为 NAFLD 的发生发展提供了新的 GAS5 介导的机制，表明 GAS5 可能成为 NAFLD 的潜在治疗靶点。丙氨酸氨基转移酶：ALT；天冬氨酸氨基转移酶：AST；酶联免疫吸附试验：ELISA；肝细胞癌：HCC；高脂肪饮食：HFD；长链非编码 RNA：LncRNA；长链非编码 RNA GAS5：GAS5；微小 RNA：miRNA；非酒精性脂肪性肝病：NAFLD；实时定量逆转录聚合酶链反应：RT-qPCRs；siRNA 阴性对照：si-NC；总胆固醇：TC；甘油三酯：TG。
