P18/Stathmin1 is regulated by miR-31 in ovarian cancer in response to taxane.
P18/Stathmin1 is regulated by miR-31 in ovarian cancer in response to taxane.
复制标题
P18/Stathmin1受卵巢癌的miR-31调节，以响应紫杉烷。
DOI：
10.18632/oncoscience.143
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Sakuragi N
中科院分区：
文献类型：
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作者：
Hassan MK;Watari H;Mitamura T;Mohamed Z;El-Khamisy SF;Ohba Y;Sakuragi N
据报道，MicroRNAs （miRNAs）在许多肿瘤中调控化疗耐药的发展。STMN1是一种微管解聚分子，参与化学反应；然而，其调控机制尚不清楚。本研究中，免疫组织化学研究表明，与应答性肿瘤相比，STMN1在被定义为耐药肿瘤的卵巢癌组织中显著上调。STMN1水平在化疗耐药卵巢癌细胞（KF- tx）中较亲本细胞（KF）升高。siRNA靶向STMN1可恢复KF-TX细胞紫杉烷敏感性。从KF/KF- tx细胞组中筛选miRNA谱，然后进行基于生物信息学的预测，发现miR-31可能是STMN1的可能调节因子。在所使用的细胞组中，通过定量RT-PCR验证miR-31的下调。在KF-TX细胞中过表达miR-31 （KF-TX-miR-31）可显著恢复化学反应并降低STMN1表达。在KF-TX-miR-31细胞中观察到STMN1还原相关的细胞特征，如增强的微管聚合和稳定性，如乙酰化微管蛋白定量，共聚焦可视化和G2期延迟，表明STMN1的功能还原。miR-31抑制含有STMN1 3 ' -未翻译区（3 ' -UTR）的报告基因构建体中的荧光素酶活性，证实miR-31直接靶向STMN1。miR-31与紫杉烷联合引入卵巢癌时具有治疗效力。
MicroRNAs (miRNAs) have been reported to regulate the development of chemoresistance in many tumors. Stathmin 1 (STMN1) is a microtubule-depolymerizing molecule, involved in chemo-response; however, the mechanism of its regulation is unknown. Herein, the immunohistochemical study indicated significant upregulation of the STMN1 in the ovarian cancer tissues defined as resistant tumors compared with those defined as responsive tumors. STMN1 level elevated in the chemoresistant ovarian cancer cells, KF-TX, compared with the parental, KF, ones. Targeting STMN1 by siRNA restored taxane-sensitivity of KF-TX cells. Screening miRNA profiles from KF/KF-TX cellular set followed by bioinformatics-based prediction, revealed that miR-31 could be a possible regulator of STMN1. Down-modulation of miR-31 was verified by quantitative RT-PCR in the cellular set used. Overexpression of miR-31 in KF-TX cells (KF-TX-miR-31) significantly restored chemo-response and reduced STMN1 expression as well. STMN1 reduction-associated cellular characteristics such as enhanced microtubule polymerization and stability, as indicated by acetylated tubulin quantification, confocal visualization, and G2 phase delay, were observed in KF-TX-miR-31 cells, indicating the functional reduction of STMN1. miR-31 suppressed the luciferase activity in reporter construct containing the STMN1 3′-untranslated region (3′-UTR), confirming that miR-31 directly targets STMN1. miR-31 has therapeutic potency when introduced into ovarian cancer, in combination with taxane.