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

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.

The Non-Coding RNA GAS5 and Its Role in Tumor Therapy-Induced Resistance

“…Several reports have also identified the connection between GAS5 and miRNAs. A recent report showed that GAS5 probably indirectly regulates miR-21, whereas its over-expression suppresses miR-21 expression and, hence, increases radiosensitivity of lung tumor cells [ 92 ]. Recently, it was also shown that miR-29-3p antagonizes GAS5 for binding PTEN [ 59 ].…”

LncRNA gas5 regulates granulosa cell apoptosis and viability following radiation by X-ray through sponging miR-205-5p and Wnt/β-catenin signaling pathway ingranulosa cell tumor of ovary

“…Researches have also discovered that lncRNAs transcripts were changed because of ultraviolet rays or ionizing radiation in peripheral blood mononuclear cell (PBMC) [28], thymocyte [29] and melanocyte [30]. LncRNA gas5 was discovered in various cancers to play a regulator in radiotherapy efficacy [31][32][33][34][35]. Therefore, we researched the role of gas5 in GCTO regarding radiation in vitro.…”

LncRNA gas5 regulates granulosa cell apoptosis and viability following radiation by x-ray via sponging miR-205- 5p and Wnt/β-catenin signaling pathway in granulosa cell tumor of ovary

“…Researches have also discovered that lncRNAs transcripts were changed because of ultraviolet rays or ionizing radiation in peripheral blood mononuclear cell (PBMC) [28], thymocyte [29] and melanocyte [30]. LncRNA gas5 was discovered in various cancers to play a regulatory role in radiotherapy efficacy [31][32][33][34][35]. This explains why the role of gas5 in GCTO regarding radiation in vitro was investigated.…”