MiR-19b通过PTEN/AKT信号通路调控胰腺癌细胞厄洛替尼化疗敏感性
MiR-19b involved in the regulation of sensitivity of pancreatic cancer cells to erlotinib by regulation PTEN/AKT pathway
目的：探索miR-19b对胰腺癌细胞生物学功能及厄洛替尼化疗敏感性的调控作用及机制。方法：通过CCK8法检测miR-19b表达水平对胰腺癌MiaPaCa-2细胞增殖、厄洛替尼化疗敏感性的调控作用。通过双萤光素酶报告基因实验明确miR-19b的作用靶点。通过Western blot检测靶基因及下游信号分子的蛋白表达水平。结果：通过转染mimics上调miR-19b表达水平，促进胰腺癌MiaPaCa-2细胞增殖，抑制厄洛替尼化疗敏感性，抑制厄洛替尼诱导的细胞凋亡。通过转染inhibitor下调miR-19b，结果相反。双萤光素酶报告基因实验发现PTEN是miR-19b的一个靶基因。上调miR-19b表达水平抑制PTEN蛋白表达，但不影响PTEN mRNA的表达水平，并增加下游分子p-AKT, p-BAD和 CCND1蛋白表达水平，抑制P27的蛋白表达水平；下调miR-19b的表达水平，可以观察到相反的结果。结论：MiR-19b通过调控PTEN/AKT信号通路参与胰腺癌细胞厄洛替尼化疗耐药调控。MiR-19b有望成为一个新的分子治疗靶点。
Objective: This study aimed to investigate the role of miR-19b in regulation of the sensitivity of pancreatic cancer cells to erlotinib.Methods: The effects of miR-19b on proliferation and chemosensitivity of erlotinib were evaluated by CCK-8 assay. Dual-luciferase reporter assays were used to verify the candidate genes. Protein levels were detected by western blot.Results: Upregulation of miR-19b in MiaPaCa-2 pancreatic cancer cell lines promoted proliferation, decreased the sensitivity of cells to erlotinib. Opposite effects were observed after downregulation of miR-19b. The dual-luciferase reporter assay verified that PTEN was a direct target of miR-19b. Upregulation of miR-497 decreased the expression of PTEN protein without any effect on PTEN mRNA expression. In addition, miR-497 upregulation increased the levels of p-AKT, p-BAD和 CCND1, and decreased the levels of P27. Opposite effects were observed after inhibition of miR-19b.Conclusion: MiR-19b involved in the regulation of sensitivity of pancreatic cancer cells to erlotinib by regulation PTEN/AKT pathway, which might be a new target of cancer therapy.
张太平、由磊、曹喆、徐建威、郑莲芳、赵玉沛
肿瘤学基础医学药学
胰腺癌miRNA表皮生长因子酪氨酸激酶抑制剂化疗耐药
pancreatic cancermiRNAEGFR-TKIdrug resistance
张太平,由磊,曹喆,徐建威,郑莲芳,赵玉沛.MiR-19b通过PTEN/AKT信号通路调控胰腺癌细胞厄洛替尼化疗敏感性[EB/OL].(2014-02-25)[2025-05-22].http://www.paper.edu.cn/releasepaper/content/201402-491.点此复制
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