Zabihula Baerxiaguli, Yiliyasi Mukedaisi, Lu Yanrong, Salai Adili
Department of Thoracic and Abdominal Radiotherapy, The Third Clinical Medical College (Affiliated Tumor Hospital) of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Department of Thoracic Surgery, The Third Clinical Medical College (Affiliated Tumor Hospital) of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Oncol Lett. 2019 Sep;18(3):3170-3176. doi: 10.3892/ol.2019.10636. Epub 2019 Jul 18.
The present study aimed to investigate whether microRNA (miR)-490-3p can regulate MAPK1 expression, increase proliferation of esophageal squamous cell carcinoma (ESCC) and reduce ESCC cell apoptosis. The Cancer Genome Atlas (TCGA) database was used to explore the functional role of miR-490-3p in ESCC. The expression of miR-490-3p in ESCC tissues and adjacent tissues of patients with ESCC were detected by reverse transcription-quantitative PCR. The effect of miR-490-3p on ESCC cell proliferation and apoptosis were detected by cell counting kit-8 and clone formation assay, and flow cytometry, respectively. The dual luciferase reporter assay was used for detect the regulatory association between miR-490-3p and MAPK1. The TCGA dataset demonstrated that miR-490-3p expression was reduced in ESCC tissues compared with normal tissue. The expression of miR-490-3p was also lower in ESCC tissues compared with adjacent tissues. The expression of miR-490-3p in patients with stage III and IV ESCC were significantly lower than those in stage I and II. In patients with tumor >3 cm, miR-490-3p expression was lower than in patients with tumor <3 cm. Gene set enrichment analysis demonstrated that miR-490-3p may essentially regulate cell apoptosis. In addition, miR-490-3p depletion in TE1 and ECA109 cell lines promoted cell proliferation and inhibited cell apoptosis. The results from dual luciferase reporter assay demonstrated that miR-490-3p may be able to degrade MAPK1. Furthermore, MAPK1 overexpression in TE1 and ECA109 cells partially reversed the effects of miR-490-3p on cell proliferation and apoptosis. Low expression of miR-490-3p may therefore promote the proliferation and inhibit the apoptosis of ESCC cells by regulating MAPK1.
本研究旨在探讨微小RNA（miR）-490-3p是否能调节丝裂原活化蛋白激酶1（MAPK1）的表达，促进食管鳞状细胞癌（ESCC）增殖并减少ESCC细胞凋亡。利用癌症基因组图谱（TCGA）数据库探究miR-490-3p在ESCC中的功能作用。采用逆转录定量聚合酶链反应检测ESCC患者癌组织及癌旁组织中miR-490-3p的表达。分别采用细胞计数试剂盒-8、克隆形成实验及流式细胞术检测miR-490-3p对ESCC细胞增殖及凋亡的影响。采用双荧光素酶报告基因检测法检测miR-490-3p与MAPK1之间的调控关系。TCGA数据集显示，与正常组织相比，ESCC组织中miR-490-3p表达降低。与癌旁组织相比，ESCC组织中miR-490-3p表达也较低。III期和IV期ESCC患者中miR-490-3p表达显著低于I期和II期患者。肿瘤>3 cm的患者中，miR-490-3p表达低于肿瘤<3 cm的患者。基因集富集分析表明，miR-490-3p可能主要调节细胞凋亡。此外，TE1和ECA109细胞系中miR-490-3p缺失促进细胞增殖并抑制细胞凋亡。双荧光素酶报告基因检测结果表明，miR-490-3p可能能够降解MAPK1。此外，TE1和ECA109细胞中MAPK1过表达部分逆转了miR-490-3p对细胞增殖和凋亡的影响。因此，miR-490-3p低表达可能通过调节MAPK1促进ESCC细胞增殖并抑制其凋亡。
