Open Access

ARTICLE

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

HAOTONG SUN^1,2,#, HEYING WANG^1,2,#, YANJIE HAO^1,2, XIN LI^1,2, JUN LING^1,2, HUAN WANG^1,2, FEIMIAO WANG^1,2, FANG XU^1,2,*

1 School of Basic Medicine, Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan, 750004, China
2 Key Laboratory of Reproduction and Genetics, Ningxia Medical University, Yinchuan, 750004, China

* Corresponding Author: FANG XU. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: New Perspectives on Inflammatory Cancer Transformation)

BIOCELL 2024, 48(9), 1311-1322. https://doi.org/10.32604/biocell.2024.052451

Received 25 February 2024; Accepted 11 June 2024; Issue published 04 September 2024

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

---

Keywords

---