Targeted regulationof STAT3 by miR-29a in mediating Taxol resistance of nasopharyngeal carcinoma cell line CNE-1
Targeted regulationof STAT3 by miR-29a in mediating Taxol resistance of nasopharyngeal carcinoma cell line CNE-1
复制标题
miR-29a 靶向调控 STAT3 介导鼻咽癌细胞系 CNE-1 紫杉醇耐药。
DOI：
10.3233/cbm-170964
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发表时间：
2018-01-01
影响因子：
3.1
通讯作者：
Yan, Yongping
中科院分区：
文献类型：
--
作者：
Gao, Jie;Shao, Zhongjun;Yan, Yongping
STAT3是Janus Kinase(JAK)信号转导和转录激活因子(STAT)信号通路中的重要分子，促进多种癌基因如Bcl2的表达，与肿瘤的发生、发展和耐药密切相关。MiR-29a表达下调与鼻咽癌的发生有关。生物信息学分析表明，miR-29a与STAT3的3‘-UTR之间存在互补结合。本研究旨在探讨miR-29a在鼻咽癌CNE-1细胞STAT3调控及紫杉醇耐药中的作用。双荧光素酶报告基因检测显示miR-29a与STAT3之间存在调控关系。检测CNE-1和CNE1/Taxol耐药细胞中的罗丹明123储存库以及miR-29a、STAT3和p-STAT3的表达。用流式细胞仪检测紫杉醇作用下细胞的凋亡率和增殖细胞核抗原的表达。用miR-29a模拟物和/或si-STAT3处理CNE-1/Taxol细胞，检测miR-29a、STAT3和p-STAT3的表达及细胞凋亡情况。CCK-8比色法检测细胞增殖情况。MIR-29a抑制STAT3的表达。与CNE-1细胞相比，CNE-2/Taxol细胞的罗丹明123库、miR-29a表达和细胞凋亡率显著降低，STAT3、p-STAT3和增殖细胞核抗原的表达显著升高。MiR-29a模拟和/或si-STAT3基因表达抑制STAT3、p-STAT3和增殖细胞核抗原的表达，抑制细胞增殖，促进细胞凋亡。MIR-29a下调与鼻咽癌细胞株CNE-1的耐药性有关，MIR-29a上调可能通过抑制STAT3和Bcl2的表达而降低鼻咽癌CNE-1细胞对紫杉醇的耐药性。
STAT3 is an important molecule in Janus kinase (JAK) signal transducer and activator of transcription (STAT) signal pathway, and facilitates expression of various oncogenic genes such as Bcl-2, thus is correlated with tumor onset, progression and drug resistance. MiR-29a down-regulation is associated with the pathogenesis of nasopharyngeal carcinoma. Bioinformatics analysis demonstrated a complementary binding between miR-29a and 3'-UTR of STAT3. This study aims to investigate the role of miR-29a in regulating STAT3, as well as in Taxol resistance of nasopharyngeal carcinoma CNE-1 cells. Dual luciferase reporter gene assay showed a regulatory relationship between miR-29a and STAT3. Rhodamine 123 repository in CNE-1 and CNE1/Taxol drug resistant cells was measured together with the expression of miR-29a, STAT3, and p-STAT3. Flow cytometry was used to measure cell apoptosis and PCNA expression under Taxol treatment. CNE-1/Taxol cells were treated with miR-29a mimic and or si-STAT3, followed by measuring the expression of miR-29a, STAT3, and p-STAT3 and cell apoptosis. CCK-8 assay was performed to evaluate cell proliferation. MiR-29a inhibited STAT3 expression. Significantly lower Rhodamine 123 repository, miR-29a expression and apoptosis and higher expression of STAT3, p-STAT3 and PCNA were observed in CNE-2/Taxol cells than those in CNE-1 cells. Transfection of miR-29a mimic and/or si-STAT3 decreased STAT3, p-STAT3 and PCNA expression, inhibited proliferation and promoted cell apoptosis. MiR-29a down-regulation is correlated with drug resistance of nasopharyngeal carcinoma cell line CNE-1 and MiR-29a up-regulation decreases Taxol resistance of nasopharyngeal carcinoma CNE-1 cells possibly via inhibiting STAT3 and Bcl-2 expression.