南方医科大学学报2024，Vol.44Issue(7)：1284-1296,13.DOI:10.12122/j.issn.1673-4254.2024.07.08
肿瘤相关成纤维细胞上调hsa-miR-18b-5p靶向FBXL3促进前列腺癌的增殖及转移
Tumor-associated fibroblasts promotes proliferation and migration of prostate cancer cells by suppressing FBXL3 via upregulating hsa-miR-18b-5p
摘要
Abstract
Objective To explore the mechanism of tumor-associated fibroblasts(CAFs)for regulating proliferation and migration of prostate cancer(PCa)cells.Methods We conducted a bioinformatics analysis to identify miRNAs with high expression in PCa.The proliferation,migration and hsa-miR-18b-5p expression levels were observed in PCa cells co-cultured with CAFs.We further examined hsa-miR-18b-5p expression level in 20 pairs of PCa and adjacent tissue samples and in different PCa cell lines and normal epithelial cells using RT-qPCR.In PCa cell lines C4-2 and LNCAPNC,the effects of transfection with a hsa-miR-18b-5p inhibitor on cell proliferation,migration,invasion,drug resistance,apoptosis and cell cycle were evaluated,and the effects of has-miR-18b-5p knockdown on C4-2 cell xenograft growth and mouse survival were observed in nude mice.Dual luciferase reporter gene assay was used to validate the targeting relationship between hsa-miR-18b-5p and its target genes,whose expressions were detected in PCa cells using RT-qPCR and Western blotting.Results The expression of hsa-miR-18b-5p was significantly increased in the co-culture of CAFs and PCa cell lines,which exhibited significantly enhanced proliferation and migration abilities.Transfection with has-miR-18b-5p inhibitor strongly attenuated the effect of CAFs for promoting proliferation and migration of PCa cells,and in C4-2 and LNCAP cells cultured alone,inhibition of hsa-miR-18b-5p obviously suppressed cell proliferation,migration,invasion,and drug resistance.In the tumor-bearing mice,hsa-miR-18b-5p knockdown in the transplanted cells significantly inhibited xenograft growth and increased the survival time of the mice.Target gene prediction suggested that FBXL3 was a potential target of hsa-miR-18b-5p,and dual luciferase reporter gene confirmed a binding site between them.In C4-2 and LNCAP cells,hsa-miR-18b-5p knockdown resulted in significantly increased expression levels of FBXL3.Conclusion CAFs promotes proliferation and migration of PCa cells by up-regulating hsa-miR-18b-5p to suppress FBXL3 expression.关键词
hsa-miR-18b-5p/肿瘤相关成纤维细胞/FBXL3/前列腺癌/促癌Key words
hsa-miR-18b-5p/tumor-associated fibroblasts/FBXL3/prostate cancer/promoting cancer引用本文复制引用
骆金光,陶怀祥,闻志远,陈龙,胡昊,关翰..肿瘤相关成纤维细胞上调hsa-miR-18b-5p靶向FBXL3促进前列腺癌的增殖及转移[J].南方医科大学学报,2024,44(7):1284-1296,13.基金项目
安徽省自然科学基金(2008085QH358) （2008085QH358）
安徽省高等学校自然科学研究重点项目(2023AH051942) （2023AH051942）
蚌埠医学院2023年度研究生科研创新计划项目(Byycx23114) （Byycx23114）
慢性疾病免疫学基础与临床安徽省重点实验室开放课题基金(AHIAI2022K01) （AHIAI2022K01）
