Wang Zhenglin, Liu Wei, Wang Cong, Ai Zhilong
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People's Republic of China.
Onco Targets Ther. 2020 Feb 4;13:1037-1046. doi: 10.2147/OTT.S213168. eCollection 2020.
Papillary thyroid cancer (PTC) is the most common type of thyroid cancer with an increasing morbidity. MicroRNAs (miRNAs) play the pivotal roles in PTC occurrence and development. The aim of this study was to investigate the biological functions of miR-873-5p and its underlying molecular mechanisms in PTC.
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect miR-873-5p expressions in PTC tissues and cell lines. The target gene of miR-873-5p was predicted by TargetScan and confirmed by dual-luciferase reporter assay. Furthermore, cell proliferation, migration and invasion were assessed by CCK-8, wound healing assay and transwell assay, respectively. Additionally, the expressions of CXCL16, MMP1, MMP9 and MMP13 were measured by RT-qPCR and Western blot methods, and p65, Rel-B and their phosphorylation levels were examined by Western blot.
We found that miR-873-5p expression was downregulated in PTC tissues and cell lines. Moreover, CXCL16 was identified as a target of miR-873-5p, and its expression was upregulated in PTC tissues and cells at both mRNA and protein levels. Functionally, overexpression of miR-873-5p inhibited PTC cell proliferation, migration and invasion, while co-transfection of CXCL16 overexpression plasmid reversed the anti-tumor behaviors induced by miR-873-5p. In addition, miR-873-5p overexpression suppressed the phosphorylation of p65 and Rel-B, and decreased the mRNA and protein expression of MMP1, MMP9 and MMP13, while overexpression of CXCL16 partially abrogated the effects of miR-873-5p.
MiR-873-5p functions as a tumor suppressor in PTC by inhibiting the proliferation, migration and invasion of the PTC cells via targeting CXCL16. These findings might provide a potential novel target for the therapy of PTC.
甲状腺乳头状癌（PTC）是最常见的甲状腺癌类型，其发病率呈上升趋势。微小RNA（miRNA）在PTC的发生和发展中起关键作用。本研究旨在探讨miR-873-5p在PTC中的生物学功能及其潜在的分子机制。
采用逆转录-定量聚合酶链反应（RT-qPCR）分析检测PTC组织和细胞系中miR-873-5p的表达。通过TargetScan预测miR-873-5p的靶基因，并通过双荧光素酶报告基因检测进行验证。此外，分别采用CCK-8、伤口愈合试验和Transwell试验评估细胞增殖、迁移和侵袭能力。另外，通过RT-qPCR和蛋白质印迹法检测CXCL16、MMP1、MMP9和MMP13的表达，通过蛋白质印迹法检测p65、Rel-B及其磷酸化水平。
我们发现miR-873-5p在PTC组织和细胞系中的表达下调。此外，CXCL16被鉴定为miR-873-5p的靶标，其在PTC组织和细胞中的mRNA和蛋白质水平均上调。在功能上，miR-873-5p的过表达抑制了PTC细胞的增殖、迁移和侵袭，而共转染CXCL16过表达质粒则逆转了miR-873-5p诱导的抗肿瘤行为。此外，miR-873-5p的过表达抑制了p65和Rel-B的磷酸化，并降低了MMP1、MMP9和MMP13的mRNA和蛋白质表达，而CXCL16的过表达部分消除了miR-873-5p的作用。
miR-873-5p通过靶向CXCL16抑制PTC细胞的增殖、迁移和侵袭，在PTC中发挥肿瘤抑制作用。这些发现可能为PTC的治疗提供一个潜在的新靶点。
