The Roles And Mechanism Of Cancer-associated Fibroblasts-derived Exosomal MiR-95 In Prostate Cancer Progression And Metastasis

Prostate cancer(PCa)is one of the most common cancers in the world,accounting for nearly one in five new cancer diagnoses in the United States alone.It is estimated that there will be nearly 1.3 million new cases of prostate cancer and 359,000 related deaths worldwide in 2020,making it the second most common cancer and fifth leading cause of cancer death in men.The most abundant cell type in the tumor microenvironment are cancer-associated fibroblasts(CAFs).CAFs play an important role in tumor growth and progression.Besides direct communication with cancer cells via secreted molecules or cell–cell adhesions,CAFs also indirectly affect cancer cell behavior by remodeling the extracellular matrix(ECM).MicroRNAs consist of a series of short,noncoding RNA which can selectively bind to the 3'-untranslated region(3'UTR)of downstream target mRNAs,promoting their degradation.MiRNAs have been widely studied in all kinds of physiological and pathological processes.Considering that the dysfunction of miRNAs in regulating cell growth and differentiation,miRNA can participate in the process of cancer biology,such as transfer,tumorigenesis and drug resistance.Exosomes are lipid bilayer vesicles with diameters ranging from 20 to 200 nm.Bioactive substances contained in exosomes,including nucleic acids(mRNA,miRNA,lncRNA),proteins mediate cellular behavior under physiological and pathological conditions.To date,it has been found that exosomes can mediate the malignant process of receptor tumor cells through the miRNA contained in them.Through IHC staining,we found significant differences in the expression of CAFs in prostate cancer tissues and para-carcinoma tissues.Exosomes from CAFs and NFs sources were extracted and microarray analysis was performed to screen miR-95 for further study.PCR confirmed the expression of miR-95 in different cell lines and further explored the biological function of miR-95 in prostate cancer through in vivo and in vitro functional studies.Finally,the potential downstream target genes of mir-95 were further explored and verified through the combination of target gene prediction website and GEO database,providing insights for understanding mechanisms of progression of PCa.