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抑制LC3B可增加卵巢癌细胞的化疗敏感性。

Inhibition LC3B can increase chemosensitivity of ovarian cancer cells.

作者信息

Tang Jing, Zhu Jiang, Ye Yuguang, Liu Yu, He Yan, Zhang Lei, Tang Dai, Qiao Cong, Feng Xinxin, Li Junyi, Kan Yanni, Li Xiaobo, Jin Xiaoming, Kong Dan

机构信息

1Department of Bioinformatics, Southern Medical University, Guangzhou, 510515 China.

2Department of Pathology, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin, 150081 China.

出版信息

Cancer Cell Int. 2019 Jul 29;19:199. doi: 10.1186/s12935-019-0921-z. eCollection 2019.

DOI:10.1186/s12935-019-0921-z
PMID:31384174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6664537/
Abstract

BACKGROUND

Ovarian cancer is often accompanied by the production of ascites, and patients with repeated ascites are associated with chemotherapy resistance. The previous study confirmed that the ovarian cancer patients who developed ascites after chemotherapy had elevated autophagy levels in the ascites and precipitated cells, which was positively correlated with MDR1 expression in the blood of patients.

METHODS

In order to explore the correlation between autophagy and chemoresistant, we searched TCGA and GEO database to analyze the correlation between LC3B and MDR1, and identified the targeting miRNA of LC3B. It was verified by dual luciferase that miR-204 can target LC3B. The ovarian cancer cell line and the BALB/c nude mice tumor-bearing model were selected for in vitro and in vivo verification. In vitro studies confirmed that ovarian cancer cells were more sensitive to cisplatin by inhibiting LC3B.

RESULTS

Overexpression of miR-204 reduced the expression of LC3B, Atg7, and MDR1, and promoted apoptosis. In vivo studies have also confirmed that reducing the level of autophagy in ovarian cancer cells increases the sensitivity to cisplatin.

CONCLUSIONS

It suggests that miR-204 can be used as a tumor suppressor gene and LC3B expression level can be used as a potential molecular marker to guide the diagnosis and treatment of patients with ovarian cancer.

摘要

背景

卵巢癌常伴有腹水产生，反复出现腹水的患者与化疗耐药相关。先前的研究证实，化疗后出现腹水的卵巢癌患者腹水中和沉淀细胞的自噬水平升高，这与患者血液中MDR1的表达呈正相关。

方法

为了探究自噬与化疗耐药之间的相关性，我们检索了TCGA和GEO数据库，分析LC3B与MDR1之间的相关性，并鉴定出LC3B的靶向miRNA。通过双荧光素酶验证miR-204可靶向LC3B。选用卵巢癌细胞系和BALB/c裸鼠荷瘤模型进行体外和体内验证。体外研究证实，抑制LC3B可使卵巢癌细胞对顺铂更敏感。

结果

miR-204过表达降低了LC3B、Atg7和MDR1的表达，并促进了细胞凋亡。体内研究也证实，降低卵巢癌细胞中的自噬水平可增加对顺铂的敏感性。

结论

这表明miR-204可作为一种肿瘤抑制基因，LC3B表达水平可作为指导卵巢癌患者诊断和治疗的潜在分子标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/9c4f43adf955/12935_2019_921_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/2ee1c2eee5d7/12935_2019_921_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/d6e77400e782/12935_2019_921_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/2de2498bd03b/12935_2019_921_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/fd4bf3fb505c/12935_2019_921_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/ae74f89a7897/12935_2019_921_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/33320e0351b7/12935_2019_921_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/9c4f43adf955/12935_2019_921_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/2ee1c2eee5d7/12935_2019_921_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/d6e77400e782/12935_2019_921_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/2de2498bd03b/12935_2019_921_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/fd4bf3fb505c/12935_2019_921_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/ae74f89a7897/12935_2019_921_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/33320e0351b7/12935_2019_921_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4086/6664537/9c4f43adf955/12935_2019_921_Fig7_HTML.jpg

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