Mitochondria-related miR-151a-5p reduces cellular ATP production by targeting CYTB in asthenozoospermia

被引:66
作者
Zhou, Ran [1 ,2 ]
Wang, Rong [3 ]
Qin, Yufeng [1 ,2 ]
Ji, Juan [1 ,2 ]
Xu, Miaofei [1 ,2 ]
Wu, Wei [1 ,2 ]
Chen, Minjian [1 ,2 ]
Wu, Di [2 ]
Song, Ling [2 ]
Shen, Hongbing [1 ,4 ,5 ]
Sha, Jiahao [1 ]
Miao, Dengshun [1 ,3 ]
Hu, Zhibin [1 ,4 ,5 ]
Xia, Yankai [1 ,2 ]
Lu, Chuncheng [1 ,2 ]
Wang, Xinru [1 ,2 ]
机构
[1] Nanjing Med Univ, Inst Toxicol, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Sch Publ Hlth, Key Lab Modern Toxicol, Minist Educ, Nanjing 210029, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Dept Anat Histol & Embryol, Res Ctr Bone & Stem Cells, Nanjing 210029, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing 210029, Jiangsu, Peoples R China
[5] Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing 210029, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
LOW SPERM MOTILITY; MICRORNA EXPRESSION; MUTATION C11994T; ND4; GENE; GENOME; APOPTOSIS; CANCER; BIOMARKERS; DIAGNOSIS;
D O I
10.1038/srep17743
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mitochondria, acting as the energy metabolism factory, participate in many key biological processes, including the maintenance of sperm viability. Mitochondria-related microRNA (miRNA), encoded by nuclear genome or mitochondrial genome, may play an important regulatory role in the control of mitochondrial function. To investigate the potential role of mitochondria-related miRNAs in asthenozoospermia, we adopted a strategy consisting of initial screening by TaqMan Low Density Array (TLDA) and further validation with quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Validation of the profiling results was conducted in two independent phases. Eventually, two seminal plasma miRNAs (sp-miRs) (miR-101-3p, let-7b-5p) were found to be significantly decreased, while sp-miR-151a-5p was significantly increased in severe asthenozoospermia cases compared with healthy controls. To further study their potential roles in asthenozoospermia, we then evaluated mitochondrial function of GC-2 cells transfected with these potentially functional miRNAs. Our results demonstrated that transfection with miR-151a-5p mimics decreased the mitochondrial respiratory activity. Besides, Adenosine Triphosphate (ATP) level was decreased when transfected with miR-151a-5p mimics. In addition, Cytochrome b (Cytb) mRNA and protein levels were also decreased when miR-151a-5p was overexpressed. These results indicate that miR-151a-5p may participate in the regulation of cellular respiration and ATP production through targeting Cytb.
引用
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页数:10
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