Department of Dermatology and STD, Affiliated Hospital of Beihua University, Jilin, People's Republic of China.
Department of Dermatology, Jilin City Central Hospital, Jilin, People's Republic of China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820980098. doi: 10.1177/1533033820980098.
Dysregulation of microRNA-214 (miR-214) has been indicated in different tumors. The function of miR-214 in cutaneous squamous cell carcinoma (CSCC) is yet to be deciphered. The current study aimed to investigate the specific mechanism underpinning CSCC development with the involvement of miR-214 and its putative targets.
Microarray analysis of CSCC and adjacent tissues was carried out to filter the most significant downregulated miRNA. Survival analysis of patients was subsequently implemented, followed by miRNA expression determination in CSCC cells. Gain-of-function assays were performed to evaluate its function on cellular level. The targets of the determined miRNA were predicted and their expression in CSCC and adjacent tissues was evaluated. The targeting relationship was analyzed by dual-luciferase assays. Finally, rescue experiments were conducted.
miR-214 was reduced in CSCC tissues and cells, and the survival of patients harboring overexpression of miR-214 was higher. miR-214 restoration increased CSCC cell apoptosis, while decreased proliferative, invasive and migratory activities. miR-214 interacted with vascular endothelial growth factor A (VEGFA) and B-cell CLL/lymphoma 2 (Bcl-2). VEGFA and Bcl-2, overexpressed in CSCC tissues and cells, were negatively correlated with miR-214. Moreover, VEGFA and Bcl-2 overexpression reversed the anti-tumor phenotypes of miR-214 on CSCC cells. miR-214 disrupted the Wnt/β-catenin pathway through VEGFA and Bcl-2 in the CSCC cells.
Our data demonstrates that miR-214 exerts a suppressing role in CSCC. The discovery of novel targets such as miR-214 and VEGFA/Bcl-2 may facilitate the development of therapeutic options.
miR-214 的失调已在不同肿瘤中得到证实。miR-214 在皮肤鳞状细胞癌 (CSCC) 中的功能尚待阐明。本研究旨在探讨 miR-214 及其潜在靶标参与 CSCC 发展的具体机制。
对 CSCC 和相邻组织进行微阵列分析，以筛选出最显著下调的 miRNA。随后对患者进行生存分析，然后在 CSCC 细胞中测定 miRNA 的表达。进行功能获得实验以评估其在细胞水平上的功能。预测所确定 miRNA 的靶标，并评估其在 CSCC 和相邻组织中的表达。通过双荧光素酶报告基因实验分析靶向关系。最后进行了挽救实验。
miR-214 在 CSCC 组织和细胞中减少，并且表达 miR-214 过表达的患者的生存率更高。miR-214 恢复增加了 CSCC 细胞凋亡，同时降低了增殖、侵袭和迁移活性。miR-214 与血管内皮生长因子 A (VEGFA) 和 B 细胞 CLL/淋巴瘤 2 (Bcl-2) 相互作用。CSCC 组织和细胞中过度表达的 VEGFA 和 Bcl-2 与 miR-214 呈负相关。此外，VEGFA 和 Bcl-2 的过表达逆转了 miR-214 对 CSCC 细胞的抗肿瘤表型。miR-214 通过 VEGFA 和 Bcl-2 在 CSCC 细胞中破坏了 Wnt/β-catenin 通路。
我们的数据表明，miR-214 在 CSCC 中发挥抑制作用。发现新的靶标，如 miR-214 和 VEGFA/Bcl-2，可能有助于开发治疗选择。
