Department of Head and Neck Radiotherapy (One), Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan.
Eur J Histochem. 2021 Sep 27;65(3):3295. doi: 10.4081/ejh.2021.3295.
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck, and radiotherapy is the main approach for this disease, while irradiation resistance is a huge challenge that influences radiosensitivity. This study aims to determine the role and function of miR-29a-3p and ADAM12 in the radiosensitivity of OSCC cells. The expression pattern of ADAM12 in OSCC cells was searched in TCGA database. The binding of miR-29a-3p and ADAM12 was predicted by Starbase and verified using dual luciferase reporter gene assay. The RNA or protein expressions of miR-29a-3p and ADAM12 were measured by RT-qPCR or western blot. OSCC cell lines were treated by various γ-ray irradiation dosages before the alteration on miR-29a-3p expression and on the cell viability, proliferation, migration and cell apoptosis was detected. ADAM12 was highly expressed in OSCC cells, whose expression in resistant cells was positively correlated with irradiation dosage. Overexpression of ADAM12 in OSCC cells lead to increased cell proliferation and migration ability as well as inhibited cell apoptosis. miRNAs potentially binding ADAM12 in PITA, microT, miRmap and targetscan were screened, among which miR-29a-3p had the maximum differential expression levels in OSCC cells determined by RT-qPCR. Overexpression of miR-29a-3p resulted in suppressed cell viability, proliferation, migration ability and increased cell apoptosis, while this expression pattern can be partially counteracted by ADAM12 overexpression in OSCC cells. miR-29a-3p through targeting and inhibiting AMDM12 enhances the radiosensitivity of OSCC cells.
口腔鳞状细胞癌 (OSCC) 是头颈部最常见的恶性肿瘤，放疗是该病的主要治疗方法，而放疗抵抗是影响放射敏感性的巨大挑战。本研究旨在确定 miR-29a-3p 和 ADAM12 在 OSCC 细胞放射敏感性中的作用和功能。在 TCGA 数据库中搜索 ADAM12 在 OSCC 细胞中的表达模式。通过 Starbase 预测 miR-29a-3p 和 ADAM12 的结合，并通过双荧光素酶报告基因检测进行验证。通过 RT-qPCR 或 Western blot 测量 miR-29a-3p 和 ADAM12 的 RNA 或蛋白表达。在改变 miR-29a-3p 表达和检测细胞活力、增殖、迁移和细胞凋亡之前，用各种 γ 射线照射剂量处理 OSCC 细胞系。ADAM12 在 OSCC 细胞中高表达，其在耐药细胞中的表达与照射剂量呈正相关。ADAM12 在 OSCC 细胞中的过表达导致细胞增殖和迁移能力增加，细胞凋亡减少。通过 PITA、microT、miRmap 和 targetscan 筛选出可能与 ADAM12 结合的 miRNAs，其中 RT-qPCR 确定 miR-29a-3p 在 OSCC 细胞中的差异表达水平最大。过表达 miR-29a-3p 导致细胞活力、增殖、迁移能力降低，细胞凋亡增加，而在 OSCC 细胞中过表达 ADAM12 可部分逆转这种表达模式。miR-29a-3p 通过靶向和抑制 AMDM12 增强 OSCC 细胞的放射敏感性。
