Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510120, China; Department of Gastroenterology, Hernia and Abdominal Wall Surgery, The sixth affiliated Hospital, Sun Yat_Sen University, Guangzhou, 510120, China.
Biomed Pharmacother. 2019 Apr;112:108608. doi: 10.1016/j.biopha.2019.108608. Epub 2019 Feb 21.
Repulsive guidance molecules comprise a group of proteins that play an important role in carcinogenesis through interactions with their receptors, but their function in oral squamous cell carcinoma (OSCC) is unclear. Here, we investigated the potential role of the RGM family members in oral cancer pathogenesis. Our study showed that only RGMA was significantly downregulated in the OSCC tissues analyzed by TCGA and validated this finding in OSCC cells. The decreased expression of RGMA was strongly associated with the T stage and with poor prognosis. The ectopic expression of RGMA significantly inhibited the proliferation of OSCC cells both in vitro and in vivo. Moreover, we confirmed that RGMA was a target of miR-210-3p in OSCC and miR-210-3p overexpression contributed to the acceleration of OSCC growth. Further experiments revealed that HIF1A specifically interacted with the promoter of miR-210-3p and enhanced its expression. In summary, our research indicates that RGMA is regulated by the HIF1A/miR-210-3p axis and inhibits OSCC cell proliferation; thus, in the future, the development of therapies that target the HIF1A/miR-210-3p/RGMA axis may aid in the treatment of aggressive cancers.
排斥性导向分子是一组蛋白质，通过与受体相互作用，在致癌作用中发挥重要作用，但它们在口腔鳞状细胞癌（OSCC）中的功能尚不清楚。在这里，我们研究了 RGMA 家族成员在口腔癌发病机制中的潜在作用。我们的研究表明，只有 RGMA 在 TCGA 分析的 OSCC 组织中显著下调，并在 OSCC 细胞中验证了这一发现。RGMA 的表达降低与 T 分期和预后不良密切相关。RGMA 的异位表达显著抑制了 OSCC 细胞在体外和体内的增殖。此外，我们证实 RGMA 是 OSCC 中 miR-210-3p 的靶标，miR-210-3p 的过表达促进了 OSCC 的生长。进一步的实验表明，HIF1A 特异性地与 miR-210-3p 启动子相互作用并增强其表达。总之，我们的研究表明，RGMA 受 HIF1A/miR-210-3p 轴的调控，抑制 OSCC 细胞增殖；因此，未来针对 HIF1A/miR-210-3p/RGMA 轴的治疗方法的开发可能有助于治疗侵袭性癌症。
