miR‑149‑5p promotes chemotherapeutic resistance in ovarian cancer via the inactivation of the Hippo signaling pathway.
miR‑149‑5p promotes chemotherapeutic resistance in ovarian cancer via the inactivation of the Hippo signaling pathway.
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DOI：
10.3892/ijo.2018.4252
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发表时间：
2018-03
影响因子：
5.2
通讯作者：
Yao S
中科院分区：
文献类型：
--
作者：
Xu M;Xiao J;Chen M;Yuan L;Li J;Shen H;Yao S
化疗药物耐药性仍然是导致卵巢癌患者治疗失败的关键临床问题。最近出现了miRNA参与卵巢癌化疗耐药性的证据。然而，化疗耐药性和miRNAs之间的潜在分子联系在很大程度上仍然未知。在这项研究中，我们报告说，miR-149- 5 p的表达显着升高，在化疗耐药的卵巢癌组织相比，化疗敏感的卵巢癌组织。此外，miR-149- 5 p的沉默增强了卵巢癌细胞对顺铂的体外和体内化疗敏感性。相反，miR-149- 5 p的上调加重了卵巢癌细胞的化疗耐药性。我们的研究结果进一步揭示了miR-149- 5 p直接靶向Hippo信号通路的核心激酶组分，STE 20样激酶（MST）1和蛋白萨尔瓦多同源物1（SAV 1），导致TEA结构域（TEAD）转录失活。总体而言，我们的研究结果揭示了miR-149- 5 p诱导卵巢癌化疗耐药的一种新的作用机制，表明miR-149- 5 p可能作为卵巢癌化疗反应的指标和潜在的治疗靶点。
Chemotherapeutic resistance remains a critical clinical issue is responsible for treatment failure in patients with ovarian cancer. Evidence of the involvement of miRNAs in chemoresistance in ovarian cancer has been recently emerging. However, the underlying molecular links between chemoresistance and miRNAs remain largely unknown. In this study, we report that miR-149-5p expression is markedly elevated in chemoresistant ovarian cancer tissues compared with the chemosensitive ovarian cancer tissues. Furthermore, the silencing of miR-149-5p enhanced the chemosensitivity of ovarian cancer cells to cisplatin in vitro and in vivo. Conversely, the upregulation of miR-149-5p aggravated chemoresistance in ovarian cancer cells. Our results further revealed that miR-149-5p directly targeted the core kinase components of the Hippo signaling pathway, STE20-like kinase (MST)1 and protein salvador homolog 1 (SAV1), resulting in the inactivation of TEA domain (TEAD) transcription. On the whole, our findings reveal a novel mechanism of of action miR-149-5p in inducing chemotherapeutic resistance in ovarian cancer, indicating that miR-149-5p may serve as a chemotherapeutic response indicator and a potential therapeutic target in ovarian cancer.
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