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Published on: July 20, 2019
NFYA Activates REG1A Expression to Promote Malignant Progression and Chemosensitivity in Rectal Cancer
Xiaolu Zhai1, Mei Hua1, Ying Chen1
1Department of Oncology, Nantong First People's Hospital and Affiliated Hospital 2 of Nantong University, Nantong, China.
Objective:
This study aimed to investigate the molecular mechanisms of rectal cancer (RC) progression and provide new insights for its treatment.
Methods:
The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER) databases, and the UALCAN platform were used to predict gene expression and correlations. The JASPAR database was used to predict transcription factors. Quantitative polymerase chain reaction (qPCR) and western blot (WB) were performed to detect gene and protein expression. Cell viability was measured using the cell counting kit-8 (CCK-8). Transcription factor-promoter interactions were examined through chromatin immunoprecipitation (ChIP) and the dual-luciferase reporter assay (DLR assay). Transcription factor-gene interactions were validated in vivo. The stats and ggplot2 packages in R were used for analysis and visualization.
Results:
Regenerating islet-derived protein 1 alpha (REG1A) was significantly associated with RC malignant progression and was the most markedly upregulated. REG1A expression was elevated in RC patient tissues and cells. REG1A knockdown reduced RC cell survival and increased phosphorylated H2A histone family member X (γH2AX) levels under X-ray or 5-Fluorouracil (5FU). Nuclear transcription factor Y subunit alpha (NFYA) was correlated with REG1A, and NFYA knockdown decreased REG1A expression and cell survival while increasing γH2AX; REG1A reversed these effects. In vivo, NFYA knockdown reduced tumor volume, weight, and REG1A levels.
Conclusion:
NFYA promoted REG1A expression, and the NFYA-REG1A axis enhanced RC resistance to RT and CT and malignant progression.
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