Downregulation of Long Noncoding RNA CRYBG3 Enhances Radiosensitivity in Non-Small Cell Lung Cancer Depending on p53 Status

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with high recurrence and metastasis rates, and more than half of the patients diagnosed with NSCLC receive local radiotherapy. However, the intrinsic radio-resistance of cancer cells is a major barrier to effective radiotherapy for NSCLC. CRYBG3 is a long noncoding RNA (lncRNA) that was originally identified to be upregulated in NSCLC and enhanced metastasis of NSCLC cells by interacting with eEF1A1 to promote murine double minute 2 (MDM2) expression. The aims of this study were to reveal the contribution of CRYBG3 to the radioresistance of NSCLC and determine whether that is associated with MDM2-p53 pathway. Therefore, CRYBG3 was stably downregulated in A549 (wild-type p53) and H1299 (deficient p53) cells by infecting short hairpin RNA (shRNA) lentiviral particles. The results showed that downregulation of CRYBG3 increased DNA damage, enhanced apoptosis and pro-apoptotic protein expression in A549 or p53-overexpressed H1299 cells but not in H1299 or p53-silenced A549 cells after X-ray irradiation. However, the contribution of CRYBG3 to radioresistance was abolished by eEF1A1 or MDM2 knockdown in A549 cells. Thus, we concluded that downregulation of CRYBG3 enhanced radiosensitivity by reducing MDM2 expression then leading to decreased MDM2-mediated degradation of p53 in wild-type p53 expressing NSCLC cells. These findings suggested that CRYBG3 can be a potential target for therapeutic intervention of certain lung cancer subtypes.

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

“…It is estimated that there are more than 100,000 lncRNAs in humans, and their number is still increasing rapidly [ 20 ]. So far, only a very small number of lncRNA functions have been annotated [ 6 , 7 ], and various methods have been developed to explore the expression, distribution, and function of lncRNAs [ 19 ]. LncRNAs may serve as tumor promotors or inhibitors by modulating the growth and development of a variety of cancer types, such as NSCLC [ 21 ].…”

“…However, lncRNAs play crucial roles in the pathogenesis, progression, and therapeutic response of diverse solid tumors and hematologic malignancies. For example, the high expression of lncRNA CRYBG3 promotes the growth, metastasis (in vitro and in vivo), and radioresistance of NSCLC cells by targeting the eEF1A1/MDM2 pathway [ 6 ]. LncRNA CARLo-5 was initially found to be specifically expressed in colon cancer, indicating its association with the invasion, metastasis, and prognosis of colon cancer [ 7 ].…”