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 transcription-polymerase 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, 6Gy) 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.