MyD88 Regulates LPS-induced NF-ĸB/MAPK Cytokines and Promotes Inflammation and Malignancy in Colorectal Cancer Cells

Abstract

Background/Aim: Inflammation may play a role in cancer initiation and progression. The molecular mechanisms by which inflammation causes colorectal cancer, remains unclear. The present study investigated a signaling pathway that affects inflammation in colorectal cancer. Materials and Methods: SW480 cells, HCT116 cells, and cells with knockdown of myeloid differentiation 88 (MyD88), and forced expression of MyD88 were treated with lipopolysaccharide (LPS; 1 μg/ml). Inflammation-related mRNA expression was analyzed by the quantitative reverse transcription polymerase chain reaction and inflammatory cytokines were detected by western blotting. The enzymelinked immunosorbent assay (ELISA) was used to quantify inflammation-related cytokines in colorectal cancer cells. Cancer cell properties were evaluated using the woundhealing assay, transwell migration assay, transwell invasion assay, colony-formation assay, and CCK-8 assay. Results: LPS up-regulated mRNA and protein levels of inflammatory factors in colorectal cancer cells. Knockdown of MyD88 inhibited LPS-induced mRNA expression and inflammatory protein expression in colorectal cancer cells. Similarly, silencing of MyD88 expression suppressed LPS-induced changes in the biological behavior of colorectal cancer cells. Silencing of MyD88 expression down-regulated expression of proteins of the LPS/nuclear factor kappa-light-chainenhancer of activated B-cells (NF-ĸB)/mitogen-activated protein kinase (MAPK) signaling pathway. Restoration of the expression of MyD88 reversed the effects in LPS-treated HCT116 cells. Conclusion: MyD88-regulated LPS/NF-ĸB/MAPK signaling pathway affects the inflammatory and biological behavior of LPS-induced colorectal cancer cells. Colorectal cancer is the fourth leading cause of cancerrelated death in the world and the fifth in China, with increasing incidence and mortality (1, 2). For more than two centuries, it has been known that inflammation and coexist. Some studies have indicated that inflammation promotes the progression of cancer (3-5). Long-term microbial infection may cause colorectal mucosa metaplasia, atypical hyperplasia and carcinoma in situ, finally leading to colorectal cancer (6, 7). However, the mechanisms by which inflammation promotes cancer progression remain unclear. Lipopolysaccharide (LPS) is present in the cell wall of Gram-negative bacteria (6, 7). Gram-negative bacterial infection leads to release of LPS in colorectal tumors in situ. Previous studies have reported that LPS can promote cell migration, invasion and the epithelial-mesenchymal transition and contribute to the progression of cancer (8-10). LPS may contribute to metastasis by accelerating cell 409 This article is freely accessible online.

3-methyadenine inhibits lipopolysaccharides-induced pulmonary inflammation at the early stage of silicosis via blocking NF-κB signaling pathway

“…Lipopolysaccharide (LPS), a compound of the cellular wall of most Gram-negative, acts as a potent initiator of inflammation and various inflammatory diseases. The interaction between LPS and toll-like receptor (TLR) actives the signaling pathways via myeloid differentiation factor (MyD) 88, resulting in the translocation of nuclear transcription factor κB (NF-κB) and the activation of its upstream regulator of mitogen-activated protein kinases (MAPKs) family, such as c-Jun-Nterminal kinase (JNK), p38 kinase, and extracellularregulated protein kinase (ERK) (Zhu et al, 2019a). NF-κB is a key transcriptional factor that involves in the regulation of inflammation, immunity, and cell fate, which is constitutively localized in the cytoplasm as an inactive p65-p50-IκB ternary complex (Mitchell et al, 2016).…”

“…It has been demonstrated that the activation of NF-κB is closely related to human pulmonary inflammation as well as disease caused by infection, injury, or autoimmune factors (Zhu et al, 2019b). Upon exposure to LPS, the heterodimer of p50 and p65 are rapidly isolated from the inhibitory subunit IκB, and then the free NF-κB translocated into the nucleus and initiates the transcription of certain genes, such as TNF-α, IL-1β, and IL-6, which could in turn further activate TLR4mediated pathways, aggravating the inflammatory response (Wu et al, 2016;(Zhu et al, 2019a). Blocking the activation of NF-κB improves the progression of lung injury, indicating the role of the NF-κB signaling pathway in the pathogenesis of the pulmonary disease (Deng et al, 2017).…”

HSA-MIR-203/MyD88 axis mediates the protective effect of hispidulin on LPS-induced apoptosis in a human renal tubular epithelial line, HK-2

“…MyD88 has been identified as a key downstream adaptor for most Toll-like regulators and IL-1 receptors (Zhu et al, 2019). Upon stimulation by LPS, MyD88 is recruited to activate its downstream inflammatory pathways (Zhu et al, 2019).…”

“…MyD88 has been identified as a key downstream adaptor for most Toll-like regulators and IL-1 receptors (Zhu et al, 2019). Upon stimulation by LPS, MyD88 is recruited to activate its downstream inflammatory pathways (Zhu et al, 2019). In HK-2 cells, it has been found that LPS-induced MyD88 activation can promote the activation of NF-ĸB and MAPK signaling pathways (Zeng et al, 2020).…”

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