LncRNA CCAT1 downregulation increases the radiosensitivity of non‐small cell lung cancer cells

Abstract

This study aims to investigate if the radiosensitivity of non-small cell lung cancer (NSCLC) cells can be regulated by long noncoding RNA (lncRNA) colon cancer associated transcript1 (CCAT1). CCAT1 was detected by quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) in NSCLC cells (A549, H1299, SK-MES1, H460, and H647) and human bronchial epithelial cells (16HBE). H460 and A549 cells were then selected for the determination of CCAT1 expression after exposure to radiation (0, 2, 4, 6 Gy) at different time points (0, 6, 12, 24 h). Colony forming assay was performed to evaluate the effects of CCAT1 siRNA or pcDNA3.1-CCAT1 vector on the radiosensitivity of H460 and A549 cells. Then, flow cytometry, western blotting and qRT-PCR were also conducted. CCAT1 was increased in NSCLC cells when compared with 16HBE cells, which was declined in a time-and dosage-dependent manner after exposure to radiation. The H460 and A549 cell colonies were decreased and the γ-H2AX expression was elevated with the increase of radiation dosage, which was more obvious in those transfected with CCAT1 siRNA. CCAT1 downregulation arrested NSCLC cells at G2/M phase. Moreover, the enhanced apoptosis of radiotherapy-treated NSCLC cells with reductions of p-p38/p38, p-ERK/ ERK, and p-JNK/JNK was promoted by siCCAT1, but it was reversed by pcDNA3.1-CCAT1 vector. Inhibiting CCAT1 regulated cell cycle, DNA damage and apoptosis of NSCLC cells, and affected MAPK pathway, eventually improving the radiosensitivity of NSCLC.

Heavy Ion-Responsive lncRNA EBLN3P Functions in the Radiosensitization of Non-Small Cell Lung Cancer Cells Mediated by TNPO1

“…The roles of lncRNAs in the efficacy of radiotherapy in non-surgically treated patients with advanced NSCLC are also gradually attracting attention. Wang et al reported that the expression of the lncRNA CCAT1, which is highly expressed in NSCLC cells, was down-regulated after irradiation, and its knockdown inhibited the mitogen-activated protein kinase pathway, which increased the radiosensitivity of NSCLC cells [22], while Ma et al demonstrated that the lncRNA LINC00460 can promote gefitinib resistance in NSCLC cells by sponging miR-769-5p to modulate EGFR [23]. The radiation resistance of lung cancer cells has long been a source of frustration for the field of radiotherapy.…”

Radio-lncRNAs: Biological Function and Potential Use as Biomarkers for Personalized Oncology

“…Downregulation of CCAT1 arrests cells at G2/M, which is believed to be the most radiosensitive moment for cells, and further promotes radiation-induced γH2AX expression, a DNA damage marker. Silencing CCAT1 may also block MAPK signaling pathways and decrease p-p38/p38, p-ERK/ERK, and p-JNK/JNK [ 33 ].…”