Open AccessLong non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells
Author(s) -
Fei Su,
Junzhao Duan,
Jie Zhu,
Hanjiang Fu,
Xiaofei Zheng,
ChangHui Ge
Publication year - 2021
Publication title -
international journal of oncology
Language(s) - Italian
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2021.5259
Subject(s) - pyroptosis , gene knockdown , biology , viability assay , cell cycle , microrna , microbiology and biotechnology , cancer research , cell , programmed cell death , apoptosis , gene , biochemistry
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.