Knockdown of MALAT1 enhances chemosensitivity of ovarian cancer cells to cisplatin through inhibiting the Notch1 signaling pathway
Knockdown of MALAT1 enhances chemosensitivity of ovarian cancer cells to cisplatin through inhibiting the Notch1 signaling pathway
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DOI：
10.1016/j.yexcr.2018.03.014
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发表时间：
2018-05-15
影响因子：
3.7
通讯作者：
Zhang, Xiao
中科院分区：
文献类型：
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作者：
Bai, Lin;Wang, Aihua;Zhang, Xiao
长链非编码rna （lncRNAs）是包括卵巢癌在内的多种肿瘤化疗耐药的关键调控因子。转移相关肺腺癌转录本1 （MALAT1）已被报道上调并参与卵巢癌的发生。本研究旨在探讨MALAT1在卵巢癌细胞化疗耐药中的作用及其潜在的分子调控机制。我们的数据表明，MALAT1和Notch1 mRNA在卵巢癌组织以及顺铂（CDDP）耐药卵巢癌细胞中表达上调。MALAT1与Notch1 mRNA表达呈正相关。MALAT1敲低可显著减弱CDDP耐药，并增强CDDP耐药卵巢癌细胞的凋亡。MALAT1敲低可增强体内cddp诱导的细胞凋亡，Box蛋白表达上调，Bcl-2蛋白表达下调。此外，MALAT1敲低抑制Notch1通路和ABCC1在cddp耐药卵巢癌细胞中的表达。MALAT1被证明与Notch1相互作用。Notchl敲低可减弱卵巢癌细胞对CDDP的耐药性，下调ABCC1蛋白的表达。综上所述，我们的研究结果表明，MALAT-1的敲低通过抑制Notchl信号通路增强了卵巢癌细胞对CDDP的化疗敏感性。
Long non-coding RNAs (lncRNAs) are critical regulators in chemoresistance of various tumors including ovarian cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to be upregulated and contributed to ovarian cancer tumorigenesis. The aim of this study was to explore the roles of MALAT1 and the underlying molecular regulatory mechanism in the chemoresistance of ovarian cancer cells. Our data demonstrated that MALAT1 and Notch1 mRNA were upregulated in ovarian cancer tissues, as well as cisplatin (CDDP)-resistant ovarian cancer cells. A positive correlation between MALAT1 and Notch1 mRNA expression was observed. MALAT1 knockdown significantly attenuated CDDP resistance, and enhanced CDDP-induced apoptosis in CDDP-resistant ovarian cancer cells. MALAT1 knockdown enhanced CDDP-induced apoptosis in vivo, as indicated by upregulation of Box protein expression and downregulation of Bcl-2 protein expression. Additionally, MALAT1 knockdown inhibited the Notch1 pathway and ABCC1 expression in CDDP-resistant ovarian cancer cells. MALAT1 was demonstrated to interact with Notch1. Notchl knockdown attenuated CDDP resistance, and downregulated the protein expression of ABCC1 in ovarian cancer cells. Taken together, our findings suggested that knockdown of MALAT-1 enhanced chemosensitivity of ovarian cancer cells to CDDP through inhibiting Notchl signaling pathway.