TY  - EJOU
AU  - SUN, HAOTONG 
AU  - WANG, HEYING 
AU  - HAO, YANJIE 
AU  - LI, XIN 
AU  - LING, JUN 
AU  - WANG, HUAN 
AU  - WANG, FEIMIAO 
AU  - XU, FANG 

TI  - MAD2L2 overexpression attenuates the effects of TNF-α-induced migration and invasion capabilities in colorectal cancer cells
T2  - BIOCELL

PY  - 2024
VL  - 48
IS  - 9
SN  - 1667-5746

AB  -  <b>Background:</b> Colorectal cancer is a major global health concern, exacerbated by tumor necrosis factor-alpha(TNF-α) and its role in inflammation, with the effects of Mitotic Arrest Deficient 2 Like 2 (MAD2L2) in this context still unclear. <b>Methods:</b> The colorectal carcinoma cell lines HCT116 and SW620 were exposed to TNF-α for a period of 24 h to instigate an inflammatory response. Subsequent assessments were conducted to measure the expression of inflammatory cytokines, the activity within the p38 mitogen-activated protein kinase (p38 MAPK) and Phosphoinositide 3-Kinase/AKT Serine/Threonine Kinase pathway (PI3K/AKT) signaling cascades. Transcriptome sequencing and subsequent integrative analysis with the Cancer Genome Atlas (TCGA) program database revealed a significant downregulation of the key factor MAD2L2. Enhancement of MAD2L2 expression was facilitated via lentiviral vector-mediated transfection. The influence of this overexpression on TNF-α-prompted inflammation, intracellular signaling pathways, and the migratory and invasive behaviors of the colorectal cancer cells was then scrutinized. <b>Results:</b> TNF-α treatment significantly increased the expression of Interleukin-1 beta (IL-1β) and Interleukin-6 (IL-6), activated the MAPK p38 and PI3K/AKT signaling pathways, and enhanced cell migration and invasion. A decrease in MAD2L2 expression was observed following TNF-α treatment. However, overexpression of MAD2L2 reversed the effects of TNF-α, reducing IL-1β and IL-6 levels, attenuating PI3K/AKT pathway activation, and inhibiting cell migration and invasion. <b>Conclusions:</b> Overexpression of MAD2L2 attenuates the pro-inflammatory effects of TNF-α, suggesting that MAD2L2 plays a protective role against TNF-α-induced migration and invasion of colorectal carcinoma cells. Therefore, MAD2L2 holds potential as a therapeutic target in the treatment of colorectal cancer.
KW  - Colorectal cancer; TNF-α; MAD2L2; Migration; Invasion

DO  - 10.32604/biocell.2024.052451