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NFE2L3 Inhibition Induces Cell Cycle Arrest at the G0/G1 Phase in Colorectal Cancer Cells through Downregulating
Lihua Zhang1,2, Dong-Li Hu1,2, Baiyou Tang1,2
1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China.
Abstract:
The molecular mechanism for colorectal cancer to develop remains unelucidated. To find biomarkers related to colorectal cancer development, we analyzed the gene expression profile of 380 colorectal cancer patients and 51 healthy controls by R software. Finally, 1579 upregulated differential expression genes (DEGs) and 3218 downregulated DEGs were identified. Then, the top 20 upregulated DEGs were compared with 181 upregulated DEGs that we reported previously, and 11 overlapped DEGs were found. NFE2L3 (nuclear factor, erythroid 2-like 3) was among those overlapped DEGs and was rarely reported in colorectal cancer. Real-time polymerase chain reaction (PCR) results showed that higher NFE2L3 expression levels were identified in paired tumor samples than in paratumor samples (48 paired samples). Flow cytometry analysis revealed that the cell cycle was arrested at the G0/G1 phase after inhibition of NFE2L3 in both HCT116 and SW480 cell lines. Western blot detection showed that CCND1 and phosphorylated Rb transcriptional corepressor 1 at ser-807/811 (pRb1-ser807/811) expression levels were downregulated when NFE2L3 was inhibited in those two cell lines. A significant positive correlation was observed between NFE2L3 and CCND1 expression levels in colorectal tissue samples. These evidences indicate that downregulation of NFE2L3 induces cell cycle arrest at the G0/G1 phase through downregulation of CCND1 and pRb1-ser807/811.
Insights
Nuclear factor, erythroid 2-like 3 (NFE2L3) acts as a potential biomarker for colorectal cancer. Its downregulation induces G0/G1 cell cycle arrest by affecting CCND1 and pRb1-ser807/811 expression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The molecular mechanisms driving colorectal cancer (CRC) development are not fully understood.
- Identifying reliable biomarkers for CRC is crucial for early detection and targeted therapy.
Purpose of the Study:
- To identify novel gene expression biomarkers associated with colorectal cancer development.
- To investigate the functional role of the nuclear factor, erythroid 2-like 3 (NFE2L3) gene in colorectal cancer progression.
Main Methods:
- Gene expression profiling analysis of 380 CRC patients and 51 healthy controls using R software.
- Real-time PCR and flow cytometry to validate NFE2L3 expression and its effect on cell cycle progression.
- Western blot analysis to assess the impact of NFE2L3 inhibition on key cell cycle regulatory proteins (CCND1, pRb1-ser807/811).
Main Results:
- 1579 upregulated and 3218 downregulated differentially expressed genes (DEGs) were identified in CRC.
- NFE2L3 was identified as a significantly upregulated DEG, with higher expression in tumor tissues compared to paratumor tissues.
- Inhibition of NFE2L3 led to G0/G1 cell cycle arrest and downregulation of CCND1 and pRb1-ser807/811 in CRC cell lines.
Conclusions:
- NFE2L3 is a potential biomarker for colorectal cancer.
- Downregulation of NFE2L3 induces G0/G1 cell cycle arrest, likely through the modulation of CCND1 and pRb1-ser807/811.
- Further research into NFE2L3's role could offer new therapeutic strategies for colorectal cancer.
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