Quantitative Proteomics Reveal the Mechanism of MiR-138-5p Suppressing Cervical Cancer via Targeting ZNF385A

被引:1
作者
Peng, Qihang [1 ]
Deng, Yiting [1 ]
Li, Guopan [1 ]
Li, Jingda [1 ]
Zheng, Peng [2 ]
Xiong, Qian [3 ]
Li, Jin [1 ]
Chen, Ying [1 ]
Ge, Feng [3 ]
机构
[1] Yangtze Univ, Coll Life Sci, Jingzhou 434025, Peoples R China
[2] Wuhan Univ Sci & Technol, Coll Life Sci & Hlth, Wuhan 430081, Peoples R China
[3] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-138-5p; cervical cancer; quantitativeproteomic; ZNF385A; proliferation; migration; TUMOR-SUPPRESSOR; HPV VACCINATION; EXPRESSION; CARCINOMA; PROTEIN; MICRORNA-138; CELLS; GENE; P53; PROLIFERATION;
D O I
10.1021/acs.jproteome.4c00349
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
MicroRNAs are short, noncoding RNA molecules that exert pivotal roles in cancer development and progression by modulating various target genes. There is growing evidence that miR-138-5p is significantly involved in cervical cancer (CC). However, its precise molecular mechanism has yet to be fully understood. In the current investigation, a quantitative proteomics approach was utilized to detect possible miR-138-5p targets in HeLa cells systematically. In total, 364 proteins were downregulated, and 150 were upregulated after miR-138-5p overexpression. Bioinformatic analysis of these differentially expressed proteins (DEPs) revealed significant enrichment in several cancer-related pathways. Zinc finger protein 385A (ZNF385A) was determined as a novel direct target of miR-138-5p and discovered to facilitate the proliferation, migration, and cell cycle progression of HeLa cells. SFN and Fas cell surface death receptor(FAS) were then identified as functional downstream effectors of ZNF385A and miR-138-5p. Moreover, a tumor xenograft experiment was conducted to validate the association of miR-138-5p-ZNF385A-SFN/FAS axis with the development of CC in vivo. Our findings have collectively established a catalog of proteins mediated by miR-138-5p and have provided an in-depth comprehension of the molecular mechanisms responsible for the inhibitory effect of miR-138-5p on CC. The miR-138-5p-ZNF385A-SFN/FAS axis could also be beneficial to the identification of new therapeutic targets.
引用
收藏
页码:3659 / 3673
页数:15
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