期刊
CELL DEATH DISCOVERY
卷 8, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41420-022-00938-1
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资金
- Natural Science Foundation of CQCSTC [cstc2020jcyj-msxmX0845]
- Basic Research and Frontier Exploration Project of Chongqing Yuzhong District [20200138]
- Chongqing Young and Middle-aged Medical Professionals Cultivation Program [no.ZQNYXGDRCGZS2019008]
- Chongqing Science and Health Joint Medical Research Project [2019ZDXM028]
miR-4731-5p inhibits glycolysis and epithelial-mesenchymal transition (EMT) in breast cancer cells by suppressing PAICS-induced phosphorylation of FAK.
A wide array of microRNAs (miRNAs) is differentially expressed in breast tumors and also functions as tumor suppressors. Herein, the current study sought to unravel the function of miR-4731-5p in breast cancer progression. First, breast cancer-related miRNA and mRNA microarray data sets were retrieved for differential analyses. Subsequently, the expression patterns of miR-4731-5p, PAICS, and FAK in breast cancer tissues and cells were determined, in addition to analyses of their roles in glycometabolism, migration, invasion, epithelial-mesenchymal transition (EMT) analyzed through functional assays. Next, the targeting relation between miR-4731-5p and PAICS was validated. Xenograft tumors in nude mice were further established to reproduce and verify the in vitro findings. miR-4731-5p was poorly expressed and PAICS was highly expressed in breast cancer tissues and cells. PAICS was confirmed as a target of miR-4731-5p. Moreover, miR-4731-5p exerted an inhibitory effect on glycolysis, EMT, migration, and invasion in breast cancer cells via regulation of PAICS-dependent phosphorylation of FAK. In vivo assay further validated the significance of the miR-4731-5p/PAICS/FAK axis in vivo tumorigenesis and lung metastasis in breast cancer. Collectively, our findings indicated that miR-4731-5p inhibited breast cancer cell glycolysis and EMT through the reduction of PAICS-induced phosphorylation of FAK.
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