Effect of GADD45G on the radioresistance of nasopharyngeal carcinoma cells

Abstract

The development of radioresistance by nasopharyngeal carcinoma (NPC) cells almost always results in tumor recurrence and metastasis, making clinical treatment of the disease difficult. In this study, the mechanism of radioresistance in NPC cells was investigated. First, a gene array and quantitative reverse-transcription-PCR assays were used to screen for genes exhibiting significantly altered expression in the DNA damage signaling pathway. Based on those results, GADD45G was further studied in the context of radioresistance. A GADD45G-knockout NPC cell line (CNE-2R-KO) was constructed using CRISPR-Cas9 technology and used for a comparison of differences in radioresistance with other radiosensitive and radioresistant NPC cells, as evaluated using colony formation assays. Cell cycle changes were observed using flow cytometry. Cell proliferation and migration were measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and wound healing assays, respectively. The sequencing results revealed the successful construction of the CNE-2R-KO cell line, the radiosensitivity of which was higher than that of its parent radioresistant cell line owing to the GADD45G knockout. This was likely related to the increase in the number of cells in the G1 phase and decrease in those in the S1 phase as well as the increased cell proliferation rate and decreased migratory ability. GADD45G is associated with radioresistance in NPC cells and likely has a role in the occurrence and metastasis of NPC.

Light Emitting Diodes Irradiation Regulates miRNA-877-3p to Promote Cardiomyocyte Proliferation

“…Recent clinical researches have shown that GADD45g expression is elevated in various CMs and may serve as a biomarker of myocardial injury 43 . In addition, GADD45g plays a role in regulating proliferation in different cancers 44 . It was found that Gadd45 protein interacts with cyclin-dependent kinase 1 (Cdk1), which is a strong inhibitor of Cdk1-cyclin B1 activity, both in vivo and in vitro 45 .…”

Overexpression of GADD45g inhibits proliferation and invasion of acute myeloid leukemia cell lines with FLT3-ITD+ by downregulating the JNK pathway

“…GADD45g gene, localized on chromosome 9q22.1-q22.2, is an evolutionarily conserved small molecule encoding an 18-kDa protein that plays a critical role in cell cycle regulation, apoptosis, and DNA damage repair 5,6 . Some studies have demonstrated that the expression of GADD45g is downregulated in breast cancer 7 , esophageal squamous carcinoma 8 , and nasopharyngeal carcinoma 9 , and the mechanism involves changes in promoter methylation or post-transcriptional modi cations 10 . In addition, GADD45g overexpression signi cantly decreases tumor cell proliferation, methylation, or post-transcriptional modi cation 10 .…”