Department of Otolaryngology, College of Medicine, The First Affiliated Hospital of Zhejiang University, Hangzhou, China.
Department of Thyroid Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China.
J Clin Lab Anal. 2022 Jun;36(6):e24470. doi: 10.1002/jcla.24470. Epub 2022 May 6.
Papillary thyroid carcinoma (PTC) grows slowly but has a great risk of metastasis. MicroRNAs are well known as vital tumor-related gene regulators. In PTC, the role of miR-203a-3p and the underlying mechanisms remain not completely understood.
We conducted CCK8 assay, wound healing assay, transwell experiment and flow cytometry analyses to investigate the function of miRNA-203a-3p. The interaction of miRNA-203a-3p with its gene MAP3K1 was characterized by quantitative real-time polymerase chain reaction, western blotting and luciferase assay.
We found that the levels of miRNA-203a-3p were statistically decreased in PTC tissues. When mimics were delivered to TPC-1 and KTC-1 cells to upregulate miR-203a-3p, it was observed that cell proliferation, metastatic abilities and cell cycle process were prevented but cell apoptosis was enhanced. Furthermore, we proved the interaction between MAP3K1 and miR-203a-3p. Intriguingly, similar to miR-203a-3p mimics, siMAP3K1 showed a tumor-suppressive effect, and this effect could be reversed when miR-203a-3p was simultaneously inhibited. Finally, selected autophagy-linked proteins such as LC3 Beclin-1 were detected and found to be increased when miR-203a-3p was upregulated or MAP3K1 was inhibited.
Overall, miR-203a-3p inhibits the oncogenic characteristics of TPC-1 and KTC-1 cells via suppressing MAP3K1 and activating autophagy. Our findings might enrich the understanding and the therapeutic strategies of PTC.
甲状腺乳头状癌(PTC)生长缓慢,但转移风险很大。微小 RNA 是众所周知的重要肿瘤相关基因调控因子。在 PTC 中,miR-203a-3p 的作用及其潜在机制尚不完全清楚。
我们通过 CCK8 测定、划痕愈合实验、Transwell 实验和流式细胞术分析来研究 miRNA-203a-3p 的功能。通过定量实时聚合酶链反应、Western blot 和荧光素酶测定来表征 miRNA-203a-3p 与其基因 MAP3K1 的相互作用。
我们发现 PTC 组织中 miRNA-203a-3p 的水平明显降低。当将 mimics 递送至 TPC-1 和 KTC-1 细胞以上调 miR-203a-3p 时,观察到细胞增殖、转移能力和细胞周期过程受到抑制,但细胞凋亡增强。此外,我们证明了 MAP3K1 与 miR-203a-3p 的相互作用。有趣的是,与 miR-203a-3p mimics 相似,siMAP3K1 表现出肿瘤抑制作用,当同时抑制 miR-203a-3p 时,这种作用可以逆转。最后,检测了选定的自噬相关蛋白,如 LC3 和 Beclin-1,发现当 miR-203a-3p 上调或 MAP3K1 被抑制时,这些蛋白的表达增加。
总之,miR-203a-3p 通过抑制 MAP3K1 和激活自噬来抑制 TPC-1 和 KTC-1 细胞的致癌特性。我们的研究结果可能丰富对 PTC 的理解和治疗策略。