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剪接因子 SNRPA 与微血管侵犯相关,通过激活 NOTCH1/Snail 通路促进肝细胞癌转移,并由 circSEC62/miR-625-5p 轴介导。

Splicing factor SNRPA associated with microvascular invasion promotes hepatocellular carcinoma metastasis through activating NOTCH1/Snail pathway and is mediated by circSEC62/miR-625-5p axis.

机构信息

Fifth Department of General Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.

Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

Environ Toxicol. 2023 May;38(5):1022-1037. doi: 10.1002/tox.23745. Epub 2023 Jan 30.

Abstract

Microvascular invasion (MVI) is a crucial risk factor related to the metastasis of hepatocellular carcinoma (HCC), but the underlying mechanisms remain to be revealed. Characterizing the inherent mechanisms of MVI may aid in the development of effective treatment strategies to improve the prognosis of HCC patients with metastasis. Through the Gene Expression Omnibus (GEO) database, we identified that small nuclear ribonucleoprotein polypeptide A (SNRPA) was related to MVI in HCC. SNRPA was overexpressed in MVI-HCC and correlated with poor patient survival. Mechanistically, SNRPA promoted the epithelial-mesenchymal transition (EMT)-like process for HCC cells to accelerate metastasis by activating the NOTCH1/Snail pathway in vitro and in vivo. Importantly, circSEC62 upregulated SNRPA expression in HCC cells via miR-625-5p sponging. Taking these results together, our study identified a novel regulatory mechanism among SNRPA, miR-625-5p, circSEC62 and the NOTCH1/Snail pathway in HCC, which promoted metastasis of HCC and may provide effective suggestions for improving the prognosis of HCC patients with metastasis.

摘要

微血管侵犯 (MVI) 是与肝细胞癌 (HCC) 转移相关的关键危险因素,但潜在机制仍有待揭示。阐明 MVI 的内在机制可能有助于制定有效的治疗策略,改善有转移的 HCC 患者的预后。通过基因表达综合数据库 (GEO),我们发现小核核糖核蛋白多肽 A (SNRPA) 与 HCC 的 MVI 有关。SNRPA 在 MVI-HCC 中过度表达,并与患者生存不良相关。在机制上,SNRPA 通过体外和体内激活 NOTCH1/Snail 通路促进 HCC 细胞的上皮-间充质转化 (EMT)样过程,从而加速转移。重要的是,circSEC62 通过海绵吸附 miR-625-5p 上调 HCC 细胞中的 SNRPA 表达。综上所述,我们的研究在 HCC 中鉴定了 SNRPA、miR-625-5p、circSEC62 和 NOTCH1/Snail 通路之间的一个新的调控机制,该机制促进了 HCC 的转移,可能为改善有转移的 HCC 患者的预后提供有效的建议。

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