Xu Yanhui, Zhang Lei, Xia Lilong, Zhu Xinhai
Department of Thoracic Surgery, Zhejiang Hospital, Hangzhou, Zhejiang 310030, P.R. China.
Oncol Lett. 2021 Jun;21(6):457. doi: 10.3892/ol.2021.12718. Epub 2021 Apr 8.
Non-small cell lung cancer (NSCLC) has high morbidity and mortality rates worldwide, and tumor metastasis is generally associated with poor prognosis. Chemotherapy resistance aggravates the challenges associated with treating NSCLC. Therefore, identifying effective targets and developing therapies based on these findings could bring novel perspectives for patients with metastatic NSCLC. The expression levels of receptor tyrosine-protein kinase erbB-2 (ERBB2) are associated with NSCLC progression. Differential microRNA (miR) expression profiles have been identified in tumors and can be used to identify multiple malignant phenotypes. miR-133a-3p expression is dysregulated in a variety of tumors. However, to the best of our knowledge, the association between miR-133a-3p and the NSCLC pathogenesis process has not been demonstrated yet. The present study revealed a decrease in miR-133a-3p expression in both tissues and cell lines, which was detected using reverse transcription-quantitative (RT-q)PCR, and western blotting and RT-qPCR demonstrated ERBB2 levels were increased at both protein and mRNA levels. Bioinformatics analysis and dual-luciferase reporter assays demonstrated that ERBB2 was a direct target of miR-133a-3p. Furthermore, MTT, wound healing and Transwell assays revealed that overexpression of miR-133a-3p suppressed proliferation, invasion and migration of NSCLC cells, respectively, effects that were inhibited following ERBB2 overexpression. In addition, immunofluorescence assays demonstrated that overexpression of ERBB2 upregulated N-cadherin expression, while E-cadherin expression was downregulated. In conclusion, the present data demonstrated that miR-133a-3p acted as a tumor suppressor by negatively regulating ERBB2 expression. The miR-133a-3p/ERBB2 axis may be a potential target for the diagnosis and treatment of NSCLC in the future.
非小细胞肺癌（NSCLC）在全球范围内具有较高的发病率和死亡率，肿瘤转移通常与预后不良相关。化疗耐药加剧了NSCLC治疗的挑战。因此，确定有效靶点并基于这些发现开发治疗方法可为转移性NSCLC患者带来新的视角。受体酪氨酸蛋白激酶erbB-2（ERBB2）的表达水平与NSCLC进展相关。在肿瘤中已鉴定出差异微小RNA（miR）表达谱，可用于识别多种恶性表型。miR-133a-3p在多种肿瘤中表达失调。然而，据我们所知，miR-133a-3p与NSCLC发病机制之间的关联尚未得到证实。本研究显示，通过逆转录定量（RT-q）PCR检测发现，miR-133a-3p在组织和细胞系中的表达均降低，蛋白质印迹法和RT-qPCR显示ERBB2在蛋白质和mRNA水平均升高。生物信息学分析和双荧光素酶报告基因检测表明，ERBB2是miR-133a-3p的直接靶点。此外，MTT、伤口愈合和Transwell检测显示，miR-133a-3p的过表达分别抑制了NSCLC细胞的增殖、侵袭和迁移，ERBB2过表达后这些作用受到抑制。此外，免疫荧光检测表明，ERBB2的过表达上调了N-钙黏蛋白的表达，而下调了E-钙黏蛋白的表达。总之，本研究数据表明，miR-133a-3p通过负向调节ERBB2表达发挥肿瘤抑制作用。miR-133a-3p/ERBB2轴可能是未来NSCLC诊断和治疗的潜在靶点。
