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微小 RNA-1252-5p 受 Myb 调控,通过靶向 NEDD9 抑制胰腺癌细胞的侵袭和上皮-间充质转化。

MicroRNA-1252-5p, regulated by Myb, inhibits invasion and epithelial-mesenchymal transition of pancreatic cancer cells by targeting NEDD9.

机构信息

Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China.

Department of Hepatobiliary Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China.

出版信息

Aging (Albany NY). 2021 Jul 27;13(14):18924-18945. doi: 10.18632/aging.203344.

Abstract

MicroRNAs (miRNAs) are known to be involved in the development and progression of pancreatic cancer (PAC). The expression levels and roles of miR-1252-5p in PAC remain unclear. Quantitative real-time PCR and hybridization were used to detect miR-1252-5p expression in PAC cells and human tissues. We studied the gain and loss of function of miR-1252-5p in the PAC cell lines and . The direct targets of miR-1252-5p were analyzed using public databases and a dual-luciferase reporter assay. Expression levels of miR-1252-5p are downregulated in PAC cell lines and tissue samples, and its expression is negatively associated with adverse clinical features and poor prognosis. and experiments show that miR-1252-5p overexpression inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of PAC cells, and miR-1252-5p knockdown enhances these biological behaviors. MiR-1252-5p negatively regulates neural precursor cell expressed, developmentally downregulated 9 (NEDD9) by directly binding its 3'- untranslated region. Further mechanism research revealed that the SRC/STAT3 pathway is involved in miR-1252-5p/NEDD9 mediation of PAC's biological behaviors. We also verified that Myb inhibited miR-1252-5p by directly binding at its promoter. MiR-1252-5p may act as a tumor-suppressing miRNA in PAC and may be a potential therapeutic target for PAC patients.

摘要

微小 RNA(miRNA)已知参与胰腺癌(PAC)的发展和进展。miR-1252-5p 在 PAC 中的表达水平和作用尚不清楚。我们使用定量实时 PCR 和杂交技术检测 PAC 细胞和人组织中 miR-1252-5p 的表达。我们研究了 miR-1252-5p 在 PAC 细胞系 和 中的功能增益和缺失。使用公共数据库和双荧光素酶报告基因检测分析 miR-1252-5p 的直接靶标。miR-1252-5p 在 PAC 细胞系和组织样本中的表达水平下调,其表达与不良临床特征和预后不良呈负相关。 和 实验表明,miR-1252-5p 过表达抑制 PAC 细胞的增殖、迁移、侵袭和上皮-间充质转化,而 miR-1252-5p 下调增强这些生物学行为。miR-1252-5p 通过直接结合其 3'-非翻译区负调控神经前体细胞表达,发育下调 9(NEDD9)。进一步的机制研究表明,SRC/STAT3 通路参与了 miR-1252-5p/NEDD9 介导的 PAC 生物学行为。我们还验证了 Myb 通过直接结合其启动子抑制 miR-1252-5p。miR-1252-5p 可能在 PAC 中作为一种肿瘤抑制 miRNA,可能是 PAC 患者的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aae/8351675/d50023824923/aging-13-203344-g001.jpg

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