Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via...

Pyroptosis is mediated by gasdermins and serves a critical role in ionizing radiation (IR)‑induced damage in normal tissues, but its role in cancer radiotherapy and underlying mechanisms remains unclear. Long non‑coding (lnc) RNAs serve important roles in regulating the radiosensitivity of cancer cells. The present study aimed to investigate the mechanistic involvement of lncRNAs in IR‑induced pyroptosis in human colorectal cancer HCT116 cells. LncRNA, microRNA (miR)‑448 and gasdermin E (GSDME) levels were evaluated using reverse transcription‑quantitative polymerase chain reaction. Protein expression and activation of gasdermins were measured using western blotting. The binding association between miR‑448 and GSDME was assessed using the dual‑luciferase reporter assay. Pyroptosis was examined using phase‑contrast microscopy, flow cytometry, Cell Counting Kit‑8 assay and lactate dehydrogenase release assay. IR dose‑dependently induced GSDME‑mediated pyroptosis in HCT116 cells. GSDME was identified as a downstream target of miR‑448. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was upregulated in response to IR and enhanced GSDME expression by negatively regulating miR‑448 expression. Notably, NEAT1 knockdown suppressed IR‑induced pyroptosis, full‑length GSDME expression and GSDME cleavage compared with that in irradiated cells. In addition, NEAT1 knockdown rescued the IR‑induced decrease in cell viability in HCT116 cells. The findings of the present study indicated that lncRNA NEAT1 modulates IR‑induced pyroptosis and viability in HCT116 cells via miR‑448 by regulating the expression, but not activation of GSDME. The present study provides crucial mechanistic insight into the potential role of lncRNA NEAT1 in IR‑induced pyroptosis.