miR-100 Inhibits Cell Growth and Proliferation by Targeting HOXA1 in Nasopharyngeal Carcinoma
miR-100 Inhibits Cell Growth and Proliferation by Targeting HOXA1 in Nasopharyngeal Carcinoma
复制标题
DOI：
10.2147/ott.s228783
复制
发表时间：
2020-01-01
影响因子：
4
通讯作者：
Tang, Sanyuan
中科院分区：
文献类型：
--
作者：
He, Weifeng;Huang, Yun;Tang, Sanyuan
背景：越来越多的证据表明 miRNA 的失调在鼻咽癌（NPC）的肿瘤发生和进展中起着至关重要的作用。因此，有必要进一步研究miRNA在鼻咽癌中的功能和机制。方法：利用公开数据库分析miR-100的表达，然后使用定量RT-PCR在鼻咽癌组织和细胞系中进行测试。使用MTT和集落形成测定以及异种移植肿瘤模型来测试NPC细胞在调节miR-100表达的同时的生长和增殖能力。通过TargetScan预测miR-100的靶点，并通过荧光素酶报告基因检测、定量RT-PCR和Western blot验证miR-100的靶点。结果：鼻咽癌组织和细胞系中miR-100的表达显着降低。在体外，过表达miR-100明显抑制鼻咽癌细胞的生长和增殖，而沉默miR-100则促进鼻咽癌细胞的生长和增殖。 HOXA1（同源盒A1）被验证为miR-100的直接靶标，恢复HOXA1表达可以逆转miR-100对鼻咽癌细胞生长和增殖的抑制作用。 HOXA1 的 mRNA 和蛋白表达在 NPC 细胞系中增加。此外，miR-100的异位表达抑制体内异种移植肿瘤的生长。结论：综上所述，我们的研究结果表明miR-100可以通过靶向HOXA1抑制鼻咽癌的生长和增殖，为未来鼻咽癌患者的miRNA介导的治疗提供新的靶点。
Background: Increasing evidence indicates that the dysregulation of miRNAs plays a vital role in tumorigenesis and progression of nasopharyngeal carcinoma (NPC). Thus, it is necessary to further investigate the function and mechanism of miRNAs in NPC.Methods: miR-100 expression was analyzed using publicly available databases and then tested using quantitative RT-PCR in NPC tissues and cell lines. MTT and colony formation assays and xenograft tumor model were used to test the NPC cell growth and proliferation abilities while modulating miR-100 expression. The target of miR-100 was predicted with TargetScan and validated with luciferase reporter assay, quantitative RT-PCR, and Western blot.Results: The expression of miR-100 was significantly reduced in NPC tissues and cell lines. Overexpression of miR-100 obviously suppressed NPC cell growth and proliferation, whereas silencing miR-100 promoted NPC cell growth and proliferation in vitro. HOXA1 (homeobox A1) was validated as a direct target of miR-100, and restoring HOXA1 expression could reverse the inhibitive effect of miR-100 on NPC cell growth and proliferation. The mRNA and protein expression of HOXA1 was increased in NPC cell lines. Furthermore, ectopic expression of miR-100 inhibited xenograft tumor growth in vivo.Conclusion: Taken together, our findings suggest that miR-100 could suppress NPC growth and proliferation through targeting HOXA1, providing a novel target for the miRNA-mediated therapy for patients with NPC in the future.