Dai Yanping, Gao Xiaoqin
Department of Pathology and Pathophysiology, College of Basic Medical Science, Guizhou Medical University, Guiyang, 550004, People's Republic of China.
Center of Reproductive Medicine, Yueyang Maternity and Child Health Hospital, Yueyang, 414000, People's Republic of China.
Cancer Cell Int. 2021 Mar 2;21(1):145. doi: 10.1186/s12935-020-01686-x.
Emerging evidence continues to highlight the significant role of microRNAs (miRNAs) in the regulation of cancer growth and metastasis. Herein, the current study aimed to elucidate the role of exosomal miR-183 in prostate cancer development.
Initially, public microarray-based gene expression profiling of prostate cancer was employed to identify differentially expressed miRNAs. The putative target gene TPM1 of miR-183 was subsequently predicted, followed by the application of a luciferase reporter assay and examination of the expression patterns in prostate cancer patients and cell lines. The effects of miR-183 and TPM1 on processes such as cell proliferation, invasion and migration were evaluated using in vitro gain- and loss-of-function experiments. The effect of PC3 cells-derived exosomal miR-183 was validated in LNCaP cells. In vivo experiments were also performed to examine the effect of miR-183 on prostate tumor growth.
High expression of miR-183 accompanied with low expression of TPM1 was detected in prostate cancer. Our data indicated that miR-183 could target and downregulate TPM1, with the overexpression of miR-183 and exosomal miR-183 found to promote cell proliferation, migration, and invasion in prostate cancer. Furthermore, the tumor-promoting effect of exosome-mediated delivery of miR-183 was subsequently confirmed in a tumor xenograft model.
Taken together, the key findings of our study demonstrate that prostate cancer cell-derived exosomal miR-183 enhance prostate cancer cell proliferation, invasion and migration via the downregulation of TPM1, highlighting a promising therapeutic target against prostate cancer.
新出现的证据不断强调微小RNA（miRNA）在癌症生长和转移调控中的重要作用。在此，本研究旨在阐明外泌体miR-183在前列腺癌发展中的作用。
首先，利用基于微阵列的前列腺癌基因表达谱来鉴定差异表达的miRNA。随后预测miR-183的假定靶基因TPM1，接着应用荧光素酶报告基因检测并检查前列腺癌患者和细胞系中的表达模式。使用体外功能获得和功能丧失实验评估miR-183和TPM1对细胞增殖、侵袭和迁移等过程的影响。在LNCaP细胞中验证了PC3细胞来源的外泌体miR-183的作用。还进行了体内实验以检查miR-183对前列腺肿瘤生长的影响。
在前列腺癌中检测到miR-183高表达且TPM1低表达。我们的数据表明miR-183可以靶向并下调TPM1，发现miR-183和外泌体miR-183的过表达可促进前列腺癌细胞的增殖、迁移和侵袭。此外，在肿瘤异种移植模型中随后证实了外泌体介导的miR-183传递的促肿瘤作用。
综上所述，我们研究的关键发现表明前列腺癌细胞来源的外泌体miR-183通过下调TPM1增强前列腺癌细胞的增殖、侵袭和迁移，突出了一个有前景的前列腺癌治疗靶点。
