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ALKBH2 inhibition alleviates malignancy in colorectal cancer by regulating BMI1-mediated activation of NF-κB pathway
Bingxin Ke1, Kejun Ye2, Shaobing Cheng2
1Department of Colorectal Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Xiacheng District, Hangzhou City, 310003, Zhejiang Province, China. 1514012@zju.edu.cn.
Background:
The alkB homolog 2, alpha-ketoglutarate-dependent dioxygenase (ALKBH2) gene is involved in DNA repair and is expressed in different types of malignancies. However, the role of ALKBH2 in colorectal carcinoma (CRC) remains unclear. This study aimed to explore the potential mechanism of ALKBH2 and its function in CRC.
Methods:
The expression levels of ALKBH2 in CRC tissues and cells were determined by qRT-PCR. Following that, the role of ALKBH2 in cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in CRC cells (Caco-2 and LOVO) were assessed by Cell Counting Kit-8 (CCK-8), transwell assays, and Western blotting, respectively. The effect of ALKBH2 on B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) and downstream NF-κB pathway was determined by Western blotting and luciferase reporter assay.
Results:
The expression of ALKBH2 was significantly upregulated both in CRC tissues and cells. Further experiments demonstrated that reduction of ALKBH2 suppressed Caco-2 and LOVO cell proliferation and invasion. Moreover, ALKBH2 knockdown also suppressed EMT, which increased E-cadherin expression and reduced N-cadherin expression. Besides, ALKBH2 silencing inhibited BMI1 expression and reduced nuclear accumulation of the NF-κB p65 protein, as well as the luciferase activity of NF-κB p65. Upregulation of BMI1 reversed the effect of ALKBH2 knockdown on the proliferation and invasion in CRC cells.
Conclusions:
Our findings suggest that suppression of ALKBH2 alleviates malignancy in CRC by regulating BMI1-mediated activation of NF-κB pathway. ALKBH2 may serve as a potential treatment target for human CRC.
Insights
AlkBH2 gene suppression reduces colorectal cancer (CRC) malignancy by inhibiting BMI1 and NF-κB pathway activation. This finding highlights AlkBH2 as a potential therapeutic target for CRC treatment.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The alkB homolog 2 (ALKBH2) gene, implicated in DNA repair, is expressed in various cancers, but its role in colorectal carcinoma (CRC) is not well understood.
- Understanding ALKBH2's function in CRC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the mechanism and function of ALKBH2 in colorectal carcinoma.
- To explore the potential of ALKBH2 as a therapeutic target for CRC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure ALKBH2 expression in CRC tissues and cells.
- Cell Counting Kit-8 (CCK-8), transwell assays, and Western blotting to assess proliferation, invasion, and epithelial-mesenchymal transition (EMT).
- Western blotting and luciferase reporter assays to determine the effect of ALKBH2 on the BMI1 and NF-κB pathway.
Main Results:
- ALKBH2 expression was significantly upregulated in CRC tissues and cells.
- ALKBH2 knockdown suppressed CRC cell proliferation, invasion, and EMT, increasing E-cadherin and decreasing N-cadherin expression.
- Silencing ALKBH2 inhibited BMI1 expression, reduced NF-κB p65 nuclear accumulation, and decreased NF-κB activity. BMI1 upregulation reversed the effects of ALKBH2 knockdown.
Conclusions:
- ALKBH2 suppression alleviates CRC malignancy by regulating the BMI1-mediated activation of the NF-κB pathway.
- ALKBH2 presents a potential therapeutic target for human colorectal carcinoma.
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