Department of Infectious Diseases, The First People's Hospital of Kunshan, China.
Bioengineered. 2022 May;13(5):13011-13020. doi: 10.1080/21655979.2022.2068895.
Accumulating research have indicated that microRNAs are associated with the progression of hepatic fibrosis (HF). Nevertheless, the biological role and function of microRNA (miR)-15a in HF are still unknown. Our data revealed that miR-15a expression was decreased in TGF-β1-treated LX-2 cells and CCl-induced mouse model. Additionally, miR-15a could directly target the 3'‑untranslated region of SRY-box transcription factor 9 (SOX9) to inhibit its expression. miR-15a overexpression attenuated the viability and invasion, but enhanced apoptosis in LX-2 cells. However, miR-15a knockdown had the opposite effects. Interestingly, SOX9 overexpression reversed the changes in cell viability, invasion and apoptosis mediated by miR-15a overexpression. Moreover, the miR-15a overexpression-mediated collagen I and alpha smooth muscle actin (a-SMA) downregulation were reversed by SOX9 overexpression. Overall, miR-15a could inhibit LX-2 cell viability and HF pathogenesis by targeting SOX9 in vitro and in vivo.
越来越多的研究表明 microRNAs 与肝纤维化（HF）的进展有关。然而，miR-15a 在 HF 中的生物学作用和功能仍不清楚。我们的数据显示，miR-15a 在 TGF-β1 处理的 LX-2 细胞和 CCl 诱导的小鼠模型中表达降低。此外，miR-15a 可以直接靶向性别决定区 Y 框转录因子 9（SOX9）的 3'非翻译区，抑制其表达。miR-15a 的过表达可减弱 LX-2 细胞的活力和侵袭能力，但促进其凋亡。然而，miR-15a 的敲低则产生相反的效果。有趣的是，SOX9 的过表达逆转了 miR-15a 过表达介导的细胞活力、侵袭和凋亡的变化。此外，SOX9 的过表达逆转了 miR-15a 过表达介导的胶原 I 和α平滑肌肌动蛋白（α-SMA）的下调。总之，miR-15a 可以通过在体外和体内靶向 SOX9 抑制 LX-2 细胞活力和 HF 发病机制。
