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Shan Guang,Gu Juan,Zhou Daoping,Li Lingxun,Cheng Wei,Wang Yueping,Tang Tian,Wang Xuedong 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
Therapeutic failure in prostate cancer (PC) is believed to result from its unusually invasive and metastatic nature. Cancer-associated fibroblasts (CAFs) are essential in the tumor microenvironment. We intended to study the role of CAF-derived exosomes in the context of PC and the potential regulatory mechanism associated with miR-423-5p and GREM2. CAF-derived exosomes decreased the chemosensitivity of parental PC cells and enhanced the drug resistance of drug-resistant cells. PC-associated fibroblast-derived exosomes carrying miR-423-5p increased the resistance of PC to taxane by inhibiting GREM2 through the TGF-β pathway. Inhibition of the TGF-β pathway partially reversed the increased drug resistance in PC cells induced by CAF-derived exosomes. Inhibition of miR-423-5p enhanced the drug sensitivity of PC cells in vivo. We showed that CAF-secreted exosomal miR-423-5p promoted chemotherapy resistance in PC by targeting GREM2 through the TGF-β pathway. This study may allow the development of novel approaches for PC.