ALKBH2 inhibition alleviates malignancy in colorectal cancer by regulating BMI1-mediated activation of NF-κB pathway.

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. [ABSTRACT FROM AUTHOR]

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