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

Abstract

In recent decades, the rapid development of radiotherapy has dramatically increased the cure rate of malignant tumors. Heavy-ion radiotherapy, which is characterized by the “Bragg Peak” because of its excellent physical properties, induces extensive unrepairable DNA damage in tumor tissues, while normal tissues in the path of ion beams suffer less damage. However, there are few prognostic molecular biomarkers that can be used to assess the efficacy of heavy ion radiotherapy. In this study, we focus on non-small cell lung cancer (NSCLC) radiotherapy and use RNA sequencing and bioinformatic analysis to investigate the gene expression profiles of A549 cells exposed to X-ray or carbon ion irradiation to screen the key genes involved in the stronger tumor-killing effect induced by carbon ions. The potential ceRNA network was predicted and verified by polymerase chain amplification, western blotting analysis, colony formation assay, and apoptosis assay. The results of the experiments indicated that lncRNA EBLN3P plays a critical role in inhibiting carbon ion-induced cell proliferation and inducing apoptosis of NSCLC cells. These functions were achieved by the EBLN3P/miR-144-3p/TNPO1 (transportin-1) ceRNA network. In summary, the lncRNA EBLN3P functions as a ceRNA to mediate lung cancer inhibition induced by carbon ion irradiation by sponging miR-144-3p to regulate TNPO1 expression, indicating that EBLN3P may be a promising target for increasing the treatment efficacy of conventional radiotherapy for NSCLC.

lncRNA EBLN3P promotes proliferation and metastasis of gastric cancer cells via miR-589-5p/HIF3A

“…It has been demonstrated that lncRNA EBLN3P has crucial functions in various cancers, including liver cancer [32], osteosarcoma [14], CRC [13] and lung cancer [33]. EBLN3P silencing suppressed liver cancer cell proliferation, migration, and invasion, while lncRNA EBLN3P overproduction stimulated these cellular progresses [32].…”

Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis

“…Studies have shown that LNC EBLN3P can promote the progression of osteosarcoma and rectal cancer by regulating different ceRNA axes, and can lead to the resistance of osteosarcoma cells to methotrexate [ 24 , 25 , 26 ]. The downregulation of LNC EBLN3P using various methods (such as siRNA, shRNA silencing pathway, or carbon ion beam irradiation) can enhance the therapeutic effect by inhibiting malignant behavior of tumor cells, inducing apoptosis of tumor cells, and increasing radiation sensitivity [ 9 , 27 , 28 ]. Therefore, LNC EBLN3P is a carcinogenic factor and therapeutic target for tumors.…”

“…LNC EBLN3P has emerged as a focal point of interest, given its dysregulation in diverse malignancies such as osteosarcoma, liver cancer, and breast cancer [ 24 , 60 , 61 ]. Furthermore, in a previous study by our team, the expression of LNC EBLN3P in lung cancer cell lines was much higher than in the normal lung bronchial epithelial cell line BEAS-2B, indicating its potential as a therapeutic target in NSCLC [ 9 ]. Nevertheless, the precise targeting and inhibition strategies for LNC EBLN3P in the context of tumor eradication remain an uncharted territory, thus signifying an imperative avenue for our forthcoming investigations.…”

“…Recently, we compared the expression of lncRNAs under carbon ion and photon radiation, and found that lncRNA EBLN3P (LNC EBLN3P) was significantly reduced by carbon ion radiation but not X-ray radiation. Furthermore, our findings demonstrated that the downregulation of LNC EBLN3P could increase apoptosis and radiosensitivity in X-ray-irradiated NSCLC cells by regulating the miR-144-3p/TNPO1 axis [ 9 ]. Evidence has revealed that mitochondria are the organelles most severely damaged by ionizing radiation (IR), since, except for nuclei, they are the only organelles with their own genome (mtDNA), which is a critical target of ionizing radiation [ 10 ].…”