Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Urology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Cell Cycle. 2023 May;22(9):1101-1115. doi: 10.1080/15384101.2023.2174658. Epub 2023 Feb 5.
Circular RNAs play crucial regulatory roles in the progression of various cancers. Nevertheless, the underlying mechanisms of circRNAs in prostate cancer (PCa) proliferation and metastasis remain largely uncertain. Here, we performed circRNA microarray analyses to identify differentially expressed circRNAs in a normal prostate epithelial cell line and PCa cell lines. We found that hsa_circ_0063329 was significantly downregulated in PCa. A series of and functional assays showed that overexpression of hsa_circ_0063329 inhibits PCa cell progression, while silencing of hsa_circ_0063329 achieved the opposite effects. Mechanistically, bioinformatics analysis, RNA pulldown, RNA-seq and dual-luciferase reporter assays demonstrated that hsa_circ_0063329 exerts its effect by sponging miR-605-5p to derepress TG-interacting factor 2 (TGIF2) and inactivate the TGF-β pathway. In conclusion, hsa_circ_0063329 inhibits the proliferation and metastasis of PCa modulation of the miR-605-5p/TGIF2 axis, and targeting hsa_circ_0063329 may provide a promising treatment strategy for aggressive PCa.
环状 RNA 在各种癌症的进展中发挥着关键的调节作用。然而，环状 RNA 在前列腺癌（PCa）增殖和转移中的潜在机制在很大程度上仍不清楚。在这里，我们进行了环状 RNA 微阵列分析，以鉴定正常前列腺上皮细胞系和 PCa 细胞系中差异表达的环状 RNA。我们发现 hsa_circ_0063329 在 PCa 中显著下调。一系列的 和 功能测定表明，hsa_circ_0063329 的过表达抑制了 PCa 细胞的进展，而 hsa_circ_0063329 的沉默则产生了相反的效果。机制上，生物信息学分析、RNA 下拉、RNA-seq 和双荧光素酶报告基因测定表明，hsa_circ_0063329 通过海绵吸附 miR-605-5p 来解除 TG 相互作用因子 2（TGIF2）的抑制作用，并使 TGF-β 通路失活。总之，hsa_circ_0063329 通过 miR-605-5p/TGIF2 轴的抑制来抑制 PCa 的增殖和转移，靶向 hsa_circ_0063329 可能为侵袭性 PCa 提供一种有前途的治疗策略。
