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MicroRNA-15a 通过靶向性调控 SRY-box 转录因子 9 抑制肝星状细胞的激活和增殖。

MicroRNA-15a inhibits hepatic stellate cell activation and proliferation via targeting SRY-box transcription factor 9.

机构信息

Department of Infectious Diseases, The First People's Hospital of Kunshan, China.

出版信息

Bioengineered. 2022 May;13(5):13011-13020. doi: 10.1080/21655979.2022.2068895.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ef/9276033/207504faa1fa/KBIE_A_2068895_UF0001_OC.jpg

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