Long non‑coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR‑21/PTEN/Akt axis

Chen,Li; Ren,Ping; Zhang,Yandong; Gong,Baijuan; Yu,Dehai; Sun,Xiguang

doi:10.3892/or.2020.7467

Long non‑coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR‑21/PTEN/Akt axis

Authors:
- Li Chen
- Ping Ren
- Yandong Zhang
- Baijuan Gong
- Dehai Yu
- Xiguang Sun
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Affiliations: 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, Department of Rheumatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Department of Orthodontics, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China, The Laboratory of Cancer Precision Medicine of The First Hospital of Jilin University, Changchun, Jilin 130061, P.R. China, Hand Surgery Department, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: January 15, 2020 https://doi.org/10.3892/or.2020.7467
Pages: 897-907
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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