Meng Xin, Sun Yanfei, Liu Shiying, Mu Yanchao
Department of Hyperbaric Oxygen, The First Affiliated Hospital of China Medical University, Liaoning, Shenyang 110001, P.R. China.
Trauma Center/Burn Ward, The First Affiliated Hospital of China Medical University, Liaoning, Shenyang 110001, P.R. China.
Oncol Lett. 2021 Apr;21(4):282. doi: 10.3892/ol.2021.12543. Epub 2021 Feb 10.
Lung adenocarcinoma (LUAD) has been considered as the most common cause of cancer-associated mortality. Radiotherapy resistance is one of the main reasons for LUAD treatment failure. The microRNA (miR)-101-3p has been previously reported to function as a tumor suppressor in several types of cancer, including LUAD. The present study aimed to explore the role and mechanism of miR-101-3p on radioresistance of lung adenocarcinoma cells through bioinformatics analysis and biological experiments. Based on the analysis of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data, it was demonstrated that the expression of miR-101-3p was low in LUAD tissues compared with normal lung tissues and was associated with poor prognosis of patients with LUAD. The results of the CCK-8 assay, colony formation assay, immunofluorescence staining, caspase-3 activity assay and western blotting demonstrated that miR-101-3p overexpression sensitized LUAD cells to ionizing radiation by decreasing the abilities of LUAD cell proliferation, colony formation, DNA damage repair and increasing caspase-3 activity and apoptosis of LUAD cells following ionizing radiation. Furthermore, according to bioinformatics analysis and luciferase assay, baculoviral IAP repeat containing 5 (BIRC5) was identified as a direct target of miR-101-3p. Increased BIRC5 expression reversed the miR-101-3p-mediated increase in LUAD cell radiotherapy sensitivity. Taken together, the results of the present study demonstrated that miR-101-3p may be considered as a potential target that can enhance LUAD cell sensitivity to radiotherapy, which may provide a new strategy to improve therapy in patients with LUAD.
肺腺癌（LUAD）被认为是癌症相关死亡的最常见原因。放疗抵抗是LUAD治疗失败的主要原因之一。此前有报道称，微小RNA（miR）-101-3p在包括LUAD在内的几种癌症中发挥肿瘤抑制作用。本研究旨在通过生物信息学分析和生物学实验，探讨miR-101-3p对肺腺癌细胞放疗抵抗的作用及机制。基于基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据的分析表明，与正常肺组织相比，LUAD组织中miR-101-3p的表达较低，且与LUAD患者的不良预后相关。CCK-8检测、集落形成检测、免疫荧光染色、caspase-3活性检测和蛋白质印迹法的结果表明，miR-101-3p过表达通过降低LUAD细胞增殖、集落形成、DNA损伤修复能力，增加电离辐射后LUAD细胞的caspase-3活性和凋亡，使LUAD细胞对电离辐射敏感。此外，根据生物信息学分析和荧光素酶检测，含杆状病毒IAP重复序列5（BIRC5）被鉴定为miR-101-3p的直接靶点。BIRC5表达增加逆转了miR-101-3p介导的LUAD细胞放疗敏感性增加。综上所述，本研究结果表明，miR-101-3p可能被视为增强LUAD细胞放疗敏感性的潜在靶点，这可能为改善LUAD患者的治疗提供新策略。
