Department of Metabolic Endocrinology, Shenzhen Longhua District Central Hospital, No. 187 Guanlan Avenue, Longhua District, Shenzhen, 518110, China.
Department of Ultrasound, General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
Hum Cell. 2020 Jul;33(3):630-640. doi: 10.1007/s13577-020-00325-x. Epub 2020 Mar 4.
Aberrant expression of miR-1256 has been reported to be closely associated with the development and progression of tumors, including colon cancer and lung cancer. However, study of its expression pattern and functional role in papillary thyroid cancer (PTC) is rare. Using quantitative real time PCR analysis, we found miR-1256 was significantly down-regulated in PTC tissues and cell lines. The correlation of miR-1256 expression with clinicopathological features was statistically analyzed. The results showed miR-1256 expression was significantly correlated with tumor size (p = 0.0124) and TNM stage (p = 0.0032). Restoring miR-1256 expression significantly inhibited proliferation and cell cycle progression of PTC cells demonstrated by CCK-8 and flow cytometry assays. Luciferase reporter assay and biotin-avidin pull-down assay showed miR-1256 can directly target 5-hydroxytryptamine receptor 3A (HTR3A) in PTC cells. The expression of miR-1256 was inversely correlated with HTR3A expression in PTC tissues. Knockdown of HTR3A imitated the suppressive effects of miR-1256 in PTC cells. Ectopic expression of HTR3A can antagonize the effects of miR-1256 on PTC cells. Furthermore, the suppressive effects of miR-1256 on the expression of PCNA, CDK4, Cyclin D1, and p21 were partially reversed by HTR3A overexpression in PTC cells. In summary, our data suggested that miR-1256 could suppress PTC cellular function by targeting HTR3A, which might be a potential therapeutic target for patients with PTC.
miR-1256 的异常表达与肿瘤的发生和发展密切相关，包括结肠癌和肺癌。然而，miR-1256 在甲状腺乳头状癌（PTC）中的表达模式和功能作用研究较少。通过实时定量 PCR 分析，我们发现 miR-1256 在 PTC 组织和细胞系中显著下调。统计分析 miR-1256 表达与临床病理特征的相关性。结果表明，miR-1256 的表达与肿瘤大小（p=0.0124）和 TNM 分期（p=0.0032）显著相关。CCK-8 和流式细胞术实验表明，恢复 miR-1256 的表达可显著抑制 PTC 细胞的增殖和细胞周期进程。荧光素酶报告基因和生物素-亲和素下拉实验表明，miR-1256 可直接靶向 PTC 细胞中的 5-羟色胺受体 3A（HTR3A）。miR-1256 在 PTC 组织中的表达与 HTR3A 的表达呈负相关。在 PTC 细胞中敲低 HTR3A 可模拟 miR-1256 的抑制作用。外源性表达 HTR3A 可拮抗 miR-1256 对 PTC 细胞的作用。此外，在 PTC 细胞中，HTR3A 的过表达部分逆转了 miR-1256 对 PCNA、CDK4、Cyclin D1 和 p21 表达的抑制作用。综上所述，我们的数据表明，miR-1256 可能通过靶向 HTR3A 抑制 PTC 细胞功能，这可能是 PTC 患者的潜在治疗靶点。
