|Table of Contents|

Study on the mechanism of mitochondrial autophagy in breast cancer cells induced by Mfn2 overexpression

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 19
Page:
3670-3676
Research Field:
Publishing date:

Info

Title:
Study on the mechanism of mitochondrial autophagy in breast cancer cells induced by Mfn2 overexpression
Author(s):
MAO Xinhui; ZHANG Jianqing; WANG Zhen; ZHU Chengbin
Radiotherapy Center,Xinjiang Uygur Autonomous Region People's Hospital,Xinjiang Urumqi 830000,China.
Keywords:
breast cancer; mitochondrial fusion gene 2; mitochondria; autophagy; apoptosis
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2024.19.008
Abstract:
Objective:To explore the role and mechanism of overexpression of mitochondrial fusion gene 2(Mfn2) in inducing apoptosis of breast cancer cells.Methods:The tumor tissues and adjacent tissues of breast cancer patients were collected,and the difference of Mfn2 expression in the two tissues was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),Western Blot and immunohistochemical staining.MCF-7 cells were divided into control group,NC group,Mfn2 group and Mfn2+3-MA group,after corresponding treatment according to the groups,the cells in 4 groups were collected.The cell proliferation activity was determined by CCK-8 method,the apoptosis rate was detected by flow cytometry,the level of intracellular reactive oxygen species(ROS) was detected by DCFH-DA probe,the mitochondrial membrane potential was detected by JC-1 staining,and the protein expressions of PTEN-induced kinase 1(PINK1),E3 ubiquitin ligase(Parkin),microtubule-associated protein 1 light chain 3(LC3) Ⅱ/LC3Ⅰ and p62 were detected by Western Blot.Results:Compared with the adjacent tissues,the relative expression of Mfn2 mRNA and protein in breast cancer tissues was significantly down-regulated(P＜0.05),and the proportion of positive cells was significantly reduced(P＜0.05).The relative expression levels of Mfn2 mRNA and protein in MCF-7 cells transfected with Mfn2 recombinant overexpression plasmid were significantly higher than those in untransfected MCF-7 cells and those transfected with negative control NC recombinant plasmid(P＜0.05).Compared with the control group,the proliferation activity of MCF-7 cells in Mfn2 group was significantly decreased(P＜0.05),the apoptosis rate was significantly increased(P＜0.05),the ROS level was significantly increased(P＜0.05),and the mitochondrial membrane potential was significantly decreased(P＜0.05),the protein expression levels of PINK1,Parkin,LC3Ⅱ/LC3Ⅰ were significantly up-regulated(P＜0.05),while the protein expression level of p62 was significantly down-regulated(P＜0.05).Compared with Mfn2 group,the proliferation activity of MCF-7 cells in Mfn2+3-MA group was significantly increased(P＜0.05),the apoptosis rate was significantly decreased(P＜0.05),the ROS level was significantly decreased(P＜0.05),and the mitochondrial membrane potential was significantly increased(P＜0.05),the protein expression levels of PINK1,Parkin,LC3Ⅱ/LC3Ⅰ were significantly down-regulated and the protein expression level of p62 was significantly up-regulated(P＜0.05).Conclusion:Mfn2 expression is low in breast cancer tissues and overexpression of Mfn2 in breast cancer cells can promote apoptosis by inducing mitochondrial autophagy and play a role in tumor inhibition.

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Memo

Memo:
新疆维吾尔自治区自然科学基金项目（编号：2022D01C642）
Last Update: 2024-08-30