General Surgery, Jinhu People's Hospital, Huaian, China.
General Surgery, Lianshui County People's Hospital, Huaian, China.
Environ Toxicol. 2021 Dec;36(12):2436-2447. doi: 10.1002/tox.23356. Epub 2021 Aug 28.
RNA-binding motif protein 38 (RBM38) belongs to the RNA recognition motif family of RNA-binding proteins (RBPs). RBM38 was previously identified to suppress tumorigenesis in colorectal cancer (CRC). RBM38 was also reported to bind to the 3'UTR of phosphatase and tensin homolog gene on chromosome 10 (PTEN), a tumor suppressor involved in many cellular processes, to stabilize PTEN transcripts. In the present study, we investigated the mechanisms underlying the regulation of RBM38 in CRC. Reverse transcription quantitative polymerase chain reaction and western blotting detected the expression of RBM38, PTEN, and miR-92a-3p. Colony formation, EdU, sphere formation, Transwell invasion, and in vivo assays examined the influence of RBM38 on CRC progression. Furthermore, RNA immunoprecipitation (RIP) assay determined the binding site of RBM38 on PTEN 3'UTR. The binding of miR-92a-3p or RBM38 on PTEN 3'UTR was assessed by luciferase reporter and RIP assays. We discovered that RBM38 was downregulated in CRC cells and tissues. RBM38 repressed CRC progression in vitro and in vivo. Furthermore, RBM38 upregulated and stabilized PTEN expression. Interestingly, the overexpression of PTEN reversely attenuated the promotion of RBM38 depletion on CRC progression. Additionally, RBM38 competed with miR-92a-3p in binding to PTEN 3'UTR. In conclusion, RBM38 inhibits CRC progression by competitively binding to PTEN 3'UTR with miR-92a-3p.
RNA 结合基序蛋白 38（RBM38）属于 RNA 结合蛋白（RBPs）的 RNA 识别基序家族。RBM38 先前被鉴定为抑制结直肠癌（CRC）中的肿瘤发生。据报道，RBM38 还与染色体 10 上的磷酸酶和张力蛋白同系物基因（PTEN）的 3'UTR 结合，PTEN 是一种参与许多细胞过程的肿瘤抑制因子，可稳定 PTEN 转录本。在本研究中，我们研究了 RBM38 在 CRC 中的调节机制。逆转录定量聚合酶链反应和 Western blot 检测了 RBM38、PTEN 和 miR-92a-3p 的表达。集落形成、EdU、球体形成、Transwell 侵袭和体内实验检测了 RBM38 对 CRC 进展的影响。此外，RNA 免疫沉淀（RIP）实验确定了 RBM38 在 PTEN 3'UTR 上的结合位点。miR-92a-3p 或 RBM38 与 PTEN 3'UTR 的结合通过荧光素酶报告和 RIP 实验进行评估。我们发现 RBM38 在 CRC 细胞和组织中表达下调。RBM38 在体外和体内抑制 CRC 进展。此外，RBM38 上调并稳定了 PTEN 的表达。有趣的是，PTEN 的过表达可逆转 RBM38 耗竭对 CRC 进展的促进作用。此外，RBM38 与 miR-92a-3p 竞争结合 PTEN 3'UTR。总之，RBM38 通过与 miR-92a-3p 竞争结合 PTEN 3'UTR 来抑制 CRC 进展。
