Chen Li, Ren Ping, Zhang Yandong, Gong Baijuan, Yu Dehai, Sun Xiguang
Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Department of Oral Radiology, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Rep. 2020 Mar;43(3):897-907. doi: 10.3892/or.2020.7467. Epub 2020 Jan 15.
Radioresistance hinders the therapeutic outcomes of radiotherapy in non‑small cell lung cancer (NSCLC). Although long non‑coding RNAs (lncRNAs) have been demonstrated to participate in the regulation of multiple cell behaviors, whether they can modulate the radiosensitivity of NSCLC and the underlying molecular mechanisms have not been well investigated. In the present study, it was revealed that NSCLC NCI‑H460 cells were more sensitive to ionizing radiation (IR) than A549 cells. Using the RNA‑Seq method, four highly differentially expressed lncRNAs were identified, including the growth arrest‑specific transcript 5 (GAS5), syntaxin binding protein 5 antisense RNA 1 (STXBP5‑AS1), metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and X‑inactive specific transcript (XIST), which were predicted to play roles in the acquisition of radiosensitivity. Using real‑time quantitative PCR (qPCR), it was demonstrated that lncRNA GAS5 was significantly upregulated in NCI‑H460 cells but not in A549 cells during IR. Mechanistically, it was demonstrated that overexpression of lncRNA GAS5 decreased the level of microRNA‑21 (miR‑21). Overexpression of lncRNA GAS5 or suppression of miR‑21 markedly increased the IR‑induced cell apoptosis of A549 cells. It was also demonstrated that overexpression of lncRNA GAS5 increased PTEN expression and suppressed Akt phosphorylation through the modulation of miR‑21. Notably, it was revealed that IR enhanced the interaction between lncRNA GAS5 and the miR‑21/PTEN/Akt axis. In summary, the present findings revealed that lncRNA GAS5 has a radiosensitization effect on NSCLC, indicating the potential application of lncRNA GAS5 in NSCLC radiotherapy.
放射抗性阻碍了非小细胞肺癌（NSCLC）放疗的治疗效果。尽管长链非编码RNA（lncRNA）已被证明参与多种细胞行为的调控，但它们是否能调节NSCLC的放射敏感性及其潜在的分子机制尚未得到充分研究。在本研究中，发现NSCLC NCI-H460细胞比A549细胞对电离辐射（IR）更敏感。使用RNA-Seq方法，鉴定出四种高度差异表达的lncRNA，包括生长停滞特异性转录本5（GAS5）、 syntaxin结合蛋白5反义RNA 1（STXBP5-AS1）、转移相关肺腺癌转录本1（MALAT1）和X染色体失活特异性转录本（XIST），它们被预测在放射敏感性的获得中发挥作用。使用实时定量PCR（qPCR）证明，在IR期间，lncRNA GAS5在NCI-H460细胞中显著上调，但在A549细胞中未上调。机制上，证明lncRNA GAS5的过表达降低了微小RNA-21（miR-21）的水平。lncRNA GAS5的过表达或miR-21的抑制显著增加了IR诱导的A549细胞凋亡。还证明lncRNA GAS5的过表达通过调节miR-21增加了PTEN表达并抑制了Akt磷酸化。值得注意的是，发现IR增强了lncRNA GAS5与miR-21/PTEN/Akt轴之间的相互作用。总之，本研究结果表明lncRNA GAS5对NSCLC具有放射增敏作用，表明lncRNA GAS5在NSCLC放疗中的潜在应用。
