Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.
Keyphrases
- dna damage
- long non coding rna
- dna repair
- long noncoding rna
- dna damage response
- cell proliferation
- poor prognosis
- papillary thyroid
- circulating tumor
- oxidative stress
- signaling pathway
- protein kinase
- cell free
- single molecule
- gene expression
- early stage
- radiation therapy
- drug delivery
- transcription factor
- childhood cancer
- epithelial mesenchymal transition
- induced apoptosis
- young adults