ALKBH2 inhibition alleviates malignancy in colorectal cancer by regulating BMI1-mediated activation of NF-κB pathway.
ALKBH2 inhibition alleviates malignancy in colorectal cancer by regulating BMI1-mediated activation of NF-κB pathway.
复制标题
ALKBH2 抑制通过调节 BMI1 介导的 NF-κB 通路激活减轻结直肠癌的恶性程度
DOI：
10.1186/s12957-020-02106-0
复制
发表时间：
2020-12-10
影响因子：
3.2
通讯作者：
Cheng S
中科院分区：
文献类型：
--
作者：
Ke B;Ye K;Cheng S
背景
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.
登录
查看更多内容
影响因子：
4.1
作者：
Chen F;Tang Q;Bian K;Humulock ZT;Yang X;Jost M;Drennan CL;Essigmann JM;Li D
通讯作者：
Li D
癌蛋白 Bmi-1 通过激活 IKK-核因子-kappaB 通路，对神经胶质瘤细胞产生凋亡抵抗。
影响因子：
6
作者：
Li, Jun;Gong, Li-Yun;Li, Mengfeng
通讯作者：
Li, Mengfeng
影响因子：
2.9
作者：
Wang, Min-Cong;Li, Chun-Li;Nan, Ke-Jun
通讯作者：
Nan, Ke-Jun
影响因子：
3.4
作者：
Goldstein DA;Zeichner SB;Bartnik CM;Neustadter E;Flowers CR
通讯作者：
Flowers CR
影响因子：
50.3
作者：
Calon A;Espinet E;Palomo-Ponce S;Tauriello DV;Iglesias M;Céspedes MV;Sevillano M;Nadal C;Jung P;Zhang XH;Byrom D;Riera A;Rossell D;Mangues R;Massagué J;Sancho E;Batlle E
通讯作者：
Batlle E