Yang Nengli, Liang Yafeng, Zhu Tianqi, Long Yanxiao, Chen Zhe, Zhang Xuezheng, Jiang Liuming
Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Oncol Lett. 2021 Jun;21(6):434. doi: 10.3892/ol.2021.12695. Epub 2021 Mar 31.
MicroRNA (miR)-199a-5p expression is downregulated in a variety of malignancies, including non-small cell lung cancer (NSCLC), and its low expression is associated with a poor prognosis. However, to the best of our knowledge, the mechanism underlying miR-199a-5p downregulation in NSCLC and its target effectors remain to be elucidated. The present study revealed the downregulation of miR-199a-5p expression in NSCLC tissues and cell lines compared with in para-carcinoma tissues and a lung epithelial cell line. Further experiments indicated that the methylation levels of the miR-199a promoter were markedly higher in NSCLC tissues compared with in para-carcinoma tissues. The DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine markedly increased the expression levels of miR-199a-5p in NSCLC cells. Furthermore, it was identified that miR-199a-5p mimics transfection decreased the expression levels of A-kinase anchoring protein 1 (AKAP1) at both the mRNA and protein levels by targeting the 3' untranslated region of AKAP1 mRNA. The experiments demonstrated that miR-199a-5p overexpression inhibited the proliferation and tumorigenicity of NSCLC cells, whereas overexpression of AKAP1 partially recovered the malignant phenotypes, suggesting that AKAP1 may be a downstream effector targeted by miR-199a-5p. Collectively, the present findings indicated that miR-199a-5p may be a novel regulator of AKAP1, and that miR-199a-5p may be a potential tumor suppressor in NSCLC.
微小RNA（miR）-199a-5p在包括非小细胞肺癌（NSCLC）在内的多种恶性肿瘤中表达下调，其低表达与预后不良相关。然而，据我们所知，NSCLC中miR-199a-5p下调的机制及其靶效应分子仍有待阐明。本研究显示，与癌旁组织和肺上皮细胞系相比，NSCLC组织和细胞系中miR-199a-5p表达下调。进一步实验表明，与癌旁组织相比，NSCLC组织中miR-199a启动子的甲基化水平明显更高。DNA甲基转移酶抑制剂5-氮杂-2'-脱氧胞苷显著提高了NSCLC细胞中miR-199a-5p的表达水平。此外，研究发现，通过靶向AKAP1 mRNA的3'非翻译区，miR-199a-5p模拟物转染在mRNA和蛋白质水平上均降低了A激酶锚定蛋白1（AKAP1）的表达水平。实验表明，miR-199a-5p过表达抑制了NSCLC细胞的增殖和致瘤性，而AKAP1过表达部分恢复了恶性表型，提示AKAP1可能是miR-199a-5p的下游效应分子。总的来说，本研究结果表明，miR-199a-5p可能是AKAP1的新型调节因子，且miR-199a-5p可能是NSCLC中的潜在肿瘤抑制因子。
