Peng Gang, Liu Yi, Yang Chenxing, Shen Chenfu
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Exp Ther Med. 2022 Jan;23(1):16. doi: 10.3892/etm.2021.10938. Epub 2021 Oct 30.
Numerous microRNAs (miRNAs/miRs) have been demonstrated to serve oncogenic or suppressive roles in glioma. Exploration of the underlying molecular mechanism of miRNAs in the development and progression of glioma is beneficial for the identification of novel therapeutic targets. In the present study, the function of miR-25 in glioma progression, as well as its underlying mechanism, were investigated. It was determined that miR-25 was significantly upregulated in glioma tissues and cell lines compared with normal brain tissues and cells, respectively. Furthermore, high expression levels of miR-25 were associated with an advanced clinical stage. The knockdown of miR-25 expression significantly reduced glioma cell proliferation, migration and invasion. Cell adhesion molecule 2 (CADM2) was identified as a direct target of miR-25 in glioma cells. Moreover, CADM2 expression level was significantly downregulated and inversely correlated with miR-25 expression level in glioma tissues, indicating that the expression of CADM2 was negatively regulated by miR-25. The inhibition of CADM2 expression counteracted the effects on glioma cell proliferation, migration and invasion caused by miR-25 downregulation. Furthermore, CADM2 knockdown considerably promoted the proliferation and migration of glioma cells. In summary, the present study demonstrated that miR-25 was significantly upregulated in glioma and that it promoted glioma cell proliferation, migration and invasion, at least partially, by directly targeting CADM2. These findings expanded the understanding of the molecular mechanism that underlies glioma progression.
众多微小RNA(miRNA/miR)已被证明在胶质瘤中发挥致癌或抑制作用。探索miRNA在胶质瘤发生发展过程中的潜在分子机制,有助于确定新的治疗靶点。在本研究中,对miR-25在胶质瘤进展中的作用及其潜在机制进行了研究。结果发现,与正常脑组织和细胞相比,miR-25在胶质瘤组织和细胞系中分别显著上调。此外,miR-25的高表达水平与临床晚期相关。miR-25表达的下调显著降低了胶质瘤细胞的增殖、迁移和侵袭能力。细胞黏附分子2(CADM2)被确定为胶质瘤细胞中miR-25的直接靶点。此外,在胶质瘤组织中,CADM2表达水平显著下调,且与miR-25表达水平呈负相关,表明CADM2的表达受miR-25的负调控。抑制CADM2的表达可抵消miR-25下调对胶质瘤细胞增殖、迁移和侵袭的影响。此外,敲低CADM2可显著促进胶质瘤细胞的增殖和迁移。总之,本研究表明,miR-25在胶质瘤中显著上调,并且它至少部分地通过直接靶向CADM2促进胶质瘤细胞的增殖、迁移和侵袭。这些发现扩展了对胶质瘤进展潜在分子机制的认识。