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Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells
Wanjuan Xue1, Yongcheng Liu2, Ningning Xin3
1Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an, 716000 Shannxi, China.
Abstract:
The study is aimed at investigating the role of Nei endonuclease VIII-like1 (NEIL1) in the pathogenesis of colorectal cancer (CRC). The human CRC (HCT116 and SW480) cells were subjected to the siRNA silencing and recombinant plasmid overexpression of NEIL1. Transfection of siNEIL1 significantly inhibited the cell growth. It also increased the Bax expression levels, while it decreased the Bcl-2 expression levels in human CRC cells, leading the Bax/Bcl-2 balance toward apoptosis. Moreover, the apoptosis was promoted through the caspase-9 signaling pathway. One the other hand, high expression of NEIL1 promoted the cell viability and reduced the apoptosis, inducing the balance of Bax/Bcl-2 in the human colon cancer cells to be antiapoptotic. In addition, the caspase-9 signaling pathway inhibited apoptosis, contrary to the results obtained by downregulating NEIL1 expression. Furthermore, NEIL1 was negatively regulated by miR-7-5p, indicating that miR-7-5p inhibited the NEIL1 expression after transcription. Overexpression of miR-7-5p reversed the effects of NEIL1 on these CRC cells. In conclusion, NEIL1 promotes the proliferation of CRC cells, which is regulated negatively by miR-7-5p. These findings suggest that NEIL1 is a potential therapeutic target for CRC.
Insights
Nei endonuclease VIII-like1 (NEIL1) promotes colorectal cancer (CRC) cell proliferation. Its activity is negatively regulated by miR-7-5p, suggesting NEIL1 as a potential therapeutic target for CRC.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Colorectal cancer (CRC) pathogenesis involves complex molecular mechanisms.
- The role of DNA repair enzymes like Nei endonuclease VIII-like1 (NEIL1) in cancer is an area of active investigation.
Purpose of the Study:
- To investigate the role of NEIL1 in the pathogenesis of colorectal cancer.
- To explore the regulatory relationship between NEIL1 and miR-7-5p in CRC cells.
Main Methods:
- Utilized siRNA silencing and recombinant plasmid overexpression of NEIL1 in human CRC cell lines (HCT116 and SW480).
- Assessed cell growth, apoptosis markers (Bax, Bcl-2), and the caspase-9 signaling pathway.
- Investigated the regulatory effect of miR-7-5p on NEIL1 expression.
Main Results:
- Downregulation of NEIL1 inhibited CRC cell growth and promoted apoptosis via the caspase-9 pathway by altering the Bax/Bcl-2 balance.
- Overexpression of NEIL1 enhanced cell viability and suppressed apoptosis.
- NEIL1 expression was negatively regulated by miR-7-5p, and miR-7-5p overexpression reversed NEIL1's effects.
Conclusions:
- NEIL1 promotes colorectal cancer cell proliferation.
- miR-7-5p negatively regulates NEIL1, suggesting a tumor-suppressive role for miR-7-5p in CRC.
- NEIL1 represents a potential therapeutic target for colorectal cancer treatment.
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