miR⁃106a⁃5p靶向STAT3抑制胶质瘤细胞增殖和侵袭的机制

doi:10.3969/j.issn.1006⁃5725.2021.20.003

实用医学杂志 ›› 2021, Vol. 37 ›› Issue (20): 2580-2585.doi: 10.3969/j.issn.1006⁃5725.2021.20.003

miR⁃106a⁃5p靶向STAT3抑制胶质瘤细胞增殖和侵袭的机制

周辉1，2 李睿春2 颜大钧2 蔡东鹏2 吴文佼2 钟德泉2 姜晓丹1

1 南方医科大学珠江医院神经外科，国家临床重点专科，脑血管病诊断与治疗教育部工程研究中心，广东省普通高校脑功能修复与再生重点实验室，广东神经外科研究所（广州 510282）； 2 广东药科大学附属第一医院神经外科（广州 510080）

出版日期:2021-10-25 发布日期:2021-10-25
通讯作者: 姜晓丹 E⁃mail：jiangxiao_dan@163.com
基金资助:
国家自然科学基金面上项目（编号：81874077）；广东省医学科研基金项目（编号：A2019235）

Mechanism of inhibition of proliferation and invasion of glioma cells by miR ⁃ 106a ⁃ 5p targeting STAT3

ZHOU Hui*，LI Ruichun，YAN Dajun，CAI Dongpeng，WU Wenjiao，ZHONG Dequan，JIANG Xiaodan.

Neurosur⁃ gery Center，Zhujiang Hospital，Southern Medical University，the National Key Clinical Specialty，the Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease， Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration，the Neurosurgery Institute of Guangdong Province，Guangzhou 510282，China；* Department of Neurosurgery，the First Affiliated Hospital of Guangdong Pharmaceutical University，Guangzhou 510080，China

Online:2021-10-25 Published:2021-10-25
Contact: JIANG Xiaodan E⁃mail：jiangxiao_dan@163.com

摘要/Abstract

摘要：

目的探究 miR⁃106a⁃5p 靶向信号转导和转录激活因子 3（STAT3）调控胶质瘤细胞增殖和侵袭的机制。方法选取 2017 年 1 月至 2020 年 12 月接受再次手术治疗的脑复发胶质瘤患者肿瘤组织 15 例及癌旁脑组织（距瘤缘>1.5 cm）5 例，体外培养正常小鼠神经元细胞和胶质瘤细胞株 GL261，qPCR 检测 miR⁃106a⁃5p 水平。将构建的 miRNA⁃NC mimics、miR⁃106a⁃5p mimics、miR⁃106a 5p inhibitor 质粒转染 GL261 作为实验组，正常GL261作为Control组，qPCR检测各组细胞miR⁃106a⁃5p、STAT3表达。应用Targetsan预测和双荧光素酶基因报告验证miR⁃106a⁃5p与STAT3的靶向关系；CCK⁃8，Transwell检测各组细胞增殖和侵袭；蛋白质印迹测定凋亡相关蛋白BAX、cl⁃caspase⁃3和抑癌基因p21水平。结果 miR⁃106a⁃5p在人复发胶质瘤组织和 GL261 中表达显著低于癌旁组织和正常小鼠神经细胞（P < 0.05），相比 Control 组，miR⁃106a⁃5p mimics 组 GL261 中 miR⁃106a⁃5p 水平显著升高、STAT3 表达显著下降（P < 0.01）。miR⁃106a⁃5p inhibitor组结果相反（P < 0.05）。Targetsan预测和双荧光素酶基因报告证实了STAT3 是 miR⁃106a⁃5p 的靶基因。此外，miR⁃ 106a⁃5p mimics 组中 STAT3 表达显著下调，GL261 增殖和侵袭明显减少（P < 0.05），BAX、cl⁃caspase⁃3、p21 的表达均显著上升（P < 0.05）；miR⁃106a⁃5p inhibitor 组相反（P < 0.05）。结论 miR⁃106a⁃5p 低表达于人复发胶质瘤组织和 GL261 中，通过负调控 STAT3 表达调节胶质瘤细胞的增殖和侵袭，为研究胶质瘤的复发提供一种新的靶点。

关键词:

胶质瘤, GL261细胞, miR?106a?5p, 信号转导和转录激活因子3, 增殖, 侵袭

Abstract:

Objective To explore the mechanism of miR⁃106a⁃5p targeting signal transducer and activator of transcription 3（STAT3）in regulating the proliferation and invasion of glioma cells. Methods From January 2017 to December 2020，15 cases of tumor tissues and 5 cases of normal adjacent tissues（more than 1.5 cm away from the edge of the tumor）of patients with recurrent glioma who underwent surgical treatment were selected. Normal mouse neuron cells and glioma cell line GL261 were cultured in vitro. The expression of miR⁃106a⁃5p was detected by qPCR. An experimental group and a conctrol group were constructed. The experimental group included miRNA ⁃NC mimics，miR ⁃106a ⁃5p mimics，miR ⁃106a ⁃5p inhibitor plasmids were transfected with GL261 cells. Normally cultured GL261 cells were used as the control group.The expressions of miR⁃106a⁃5p and STAT3 in each group were detected by qPCR. Targeting relationship between miR⁃106a⁃5p and STAT3 was predicted and analyzed by the bioinformatics software and Dual luciferase assay. CCK⁃8 and Transwell chamber assay were used to detect cell proliferation activity and invasion ability of each group cells；The expressions of STAT3，apoptosis⁃related pro⁃ teins BAX，cl⁃cas⁃pase⁃3，and tumor suppressor gene p21 were detected by WB. Results The expression of miR⁃ 106a⁃5p in human recurrent glioma tissues and mouse glioma cells was significantly lower than that in paracancerous tissues and normal mouse nerve cells（P < 0.05）. Compared with that in the control group，the level of miR⁃106a⁃5p in GL261 transfected with miR⁃106a⁃5p mimics was significantly increased，while the expression of STAT3 was significantly decreased（P < 0.01）. Respectively，the expression in miR⁃106a⁃5p inhibitor group was opposite（P < 0.05）. STAT3 was the target gene of miR⁃106a⁃5p by dual luciferase assay. Compared with those in control group， the expression of STAT3，cell viability and number of invasive cells in the miR⁃106a⁃5p mimics group were signifi⁃ cantly decreased（P < 0.05），but the expression of BAX，cl ⁃caspase ⁃3 and p21 was significantly increased（P < 0.05）；However，the expression of these proteins，cell viability and number of invasive cells in the miR⁃106a⁃5p inhibitor group was the opposite correspondingly（P < 0.05）. Conclusion miR⁃106a⁃5p is low⁃expressed in human recurrent glioma tissues and GL261，and regulates the proliferation and invasion of glioma cells through negatively regulation of STAT3，which provides a new target for studying the recurrence mechanism of glioma.

Key words:

glioma, GL261 cells, miR?106a?5p, signal transducer and activator of transcription 3, proliferation, invasion

周辉, 李睿春颜大钧蔡东鹏吴文佼钟德泉姜晓丹.

miR⁃106a⁃5p靶向STAT3抑制胶质瘤细胞增殖和侵袭的机制 [J]. 实用医学杂志, 2021, 37(20): 2580-2585.

ZHOU Hui, LI Ruichun, YAN Dajun, CAI Dongpeng, WU Wenjiao, ZHONG Dequan, JIANG Xiaodan..

Mechanism of inhibition of proliferation and invasion of glioma cells by miR ⁃ 106a ⁃ 5p targeting STAT3 [J]. The Journal of Practical Medicine, 2021, 37(20): 2580-2585.

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miR⁃106a⁃5p靶向STAT3抑制胶质瘤细胞增殖和侵袭的机制

Mechanism of inhibition of proliferation and invasion of glioma cells by miR ⁃ 106a ⁃ 5p targeting STAT3

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