Department of Ophthalmology, Wuhan No. 1 Hospital, No. 215, Zhongshan Avenue, Qiaokou District, Wuhan, 430022, Hubei, China.
Sci Rep. 2024 Mar 27;14(1):7277. doi: 10.1038/s41598-023-49994-2.
MicroRNAs (miRNAs) are vital regulators of tumor pathogenesis, including that of retinoblastoma (Rb). This study investigated the functions and mechanisms of action of miR-889-3p in Rb. BMPR2 and miR-889-3p levels were assessed by quantitative reverse transcription PCR (qRT-PCR) or western blotting. Through several cell function tests, the effects of miR-889-3p and BMPR2 on cell proliferation, migration, and JNK/MAPK/ERK signaling were evaluated. The interaction between miR-889-3p and BMPR2 was investigated using a luciferase reporter assay. In vivo tumor development was investigated using a xenograft test. The association between miR-889-3p and BMPR2 expression was identified using Pearson's correlation analysis. miR-889-3p was increased in Rb cells, and miR-889-3p knockdown inhibited Rb cell proliferation, migration, and phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and ERK1/2 in vitro, as well as tumor growth in vivo. Further, they were inversely associated in Rb tissues and miR-889-3p may directly attached to the 3'-UTR of BMPR2 mRNA. Finally, the inhibition of BMPR2 inverted the negative effects of the miR-889-3p inhibitor on migration, proliferation, and activation of JNK, p38 MAPK, and ERK1/2 in Rb cells. Our results indicate that miR-889-3p, which targets BMPR2 and promotes Rb growth by controlling the JNK/MAPK/ERK pathway, is an oncogene in Rb. These results suggested that the miR-889-3p/BMPR2 axis may be a new therapeutic target for Rb.
微小 RNA（miRNA）是肿瘤发病机制的重要调节因子，包括视网膜母细胞瘤（Rb）。本研究探讨了 miR-889-3p 在 Rb 中的作用和作用机制。通过定量逆转录 PCR（qRT-PCR）或 Western blot 评估 BMPR2 和 miR-889-3p 的水平。通过几项细胞功能测试，评估了 miR-889-3p 和 BMPR2 对细胞增殖、迁移和 JNK/MAPK/ERK 信号通路的影响。通过荧光素酶报告基因检测研究了 miR-889-3p 和 BMPR2 之间的相互作用。通过异种移植试验研究体内肿瘤的发展。通过 Pearson 相关分析确定 miR-889-3p 与 BMPR2 表达之间的相关性。miR-889-3p 在 Rb 细胞中增加，miR-889-3p 敲低抑制 Rb 细胞增殖、迁移以及体外 c-Jun N-末端激酶（JNK）、p38 丝裂原活化蛋白激酶（MAPK）和 ERK1/2 的磷酸化，以及体内肿瘤生长。此外，它们在 Rb 组织中呈负相关，miR-889-3p 可能直接附着在 BMPR2 mRNA 的 3'-UTR 上。最后，BMPR2 的抑制逆转了 miR-889-3p 抑制剂对 Rb 细胞迁移、增殖和 JNK、p38 MAPK 和 ERK1/2 激活的负性影响。我们的研究结果表明，miR-889-3p 通过控制 JNK/MAPK/ERK 通路靶向 BMPR2 并促进 Rb 生长，是 Rb 中的致癌基因。这些结果表明，miR-889-3p/BMPR2 轴可能是 Rb 的一个新的治疗靶点。
