Department of Medical Oncology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of Oral and Maxillofacial Surgery, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
J Cell Mol Med. 2019 Apr;23(4):2813-2821. doi: 10.1111/jcmm.14189. Epub 2019 Feb 7.
The biological function and underlying mechanism of miR-1258 has seldom been investigated in cancer progression, including in oral squamous cell carcinoma (OSCC). In the current study, we revealed that the expression level of miR-1258 was significantly down-regulated in OSCC tissues and cell lines. Restoration of miR-1258 decreased OSCC cell growth and invasion. The luciferase and Western blot assays revealed that SP1 protein was a downstream target of miR-1258. Overexpression of SP1 dismissed miR-1258's effect on cell growth and invasion. We also revealed that c-Myb inhibited miR-1258 by directly binding at its promoter. In addition, miR-1258 inhibited PI3K/AKT and ERK signalling pathway activity. Taken together, these findings demonstrated that miR-1258 may function as a tumour-suppressive micorRNA in OSCC and suggested that miR-1258 may be a potential therapeutic target for OSCC patients.
miR-1258 在癌症进展中的生物学功能和潜在机制很少被研究过，包括口腔鳞状细胞癌（OSCC）。在本研究中，我们揭示了 miR-1258 的表达水平在 OSCC 组织和细胞系中明显下调。恢复 miR-1258 的表达水平可降低 OSCC 细胞的生长和侵袭能力。荧光素酶和 Western blot 分析表明，SP1 蛋白是 miR-1258 的下游靶标。过表达 SP1 可消除 miR-1258 对细胞生长和侵袭的影响。我们还揭示了 c-Myb 通过直接结合其启动子来抑制 miR-1258。此外，miR-1258 抑制了 PI3K/AKT 和 ERK 信号通路的活性。综上所述，这些发现表明 miR-1258 可能在 OSCC 中作为一种肿瘤抑制性 micorRNA 发挥作用，并提示 miR-1258 可能是 OSCC 患者的潜在治疗靶点。
