Transmembrane p24 trafficking protein 2 regulates inflammation through the TLR4/NF-κB signaling pathway in lung adenocarcinoma

Abstract

Background To investigate the role of transmembrane p24 trafficking protein 2 (TMED2) in lung adenocarcinoma (LUAD) and determine whether TMED2 knockdown could inhibit LUAD in vitro and in vivo. Methods TIMER2.0, Kaplan-Meier plotter, gene set enrichment analysis (GSEA), Target Gene, and pan-cancer systems were used to predict the potential function of TMED2. Western blotting and immunohistochemistry were performed to analyze TMED2 expression in different tissues or cell lines. The proliferation, development, and apoptosis of LUAD were observed using a lentivirus-mediated TMED2 knockdown. Bioinformatics and western blot analysis of TMED2 against inflammation via the TLR4/NF-κB signaling pathway were conducted. Results TMED2 expression in LUAD tumor tissues was higher than that in normal tissues and positively correlated with poor survival in lung cancer and negatively correlated with apoptosis in LUAD. The expression of TMED2 was higher in tumors or HCC827 cells. TMED2 knockdown inhibited LUAD development in vitro and in vivo and increased the levels of inflammatory factors via the TLR4/NF-κB signaling pathway. TMED2 was correlated with TME, immune score, TME-associated immune cells, their target markers, and some mechanisms and pathways, as determined using the TIMER2.0, GO, and KEGG assays. Conclusions TMED2 may regulate inflammation in LUAD through the TLR4/NF-κB signaling pathway and enhance the proliferation, development, and prognosis of LUAD by regulating inflammation, which provide a new strategy for treating LUAD by regulating inflammation.

An integrated analysis of prognostic and immune infiltrates for hub genes as potential survival indicators in patients with lung adenocarcinoma

“…A study on the advanced lung cancer inflammation index, for example, discovered that it can predict shorter overall survival not only in patients with lung adenocarcinoma, but also in patients with other tumors at a low level of expression [ 54 ]. TMED2, MOESIN, DPYSL2, and LncRNA MEG3 have been discovered to enhance the occurrence and development of patients with lung adenocarcinoma via several immune-related regulatory mechanisms [ 55 – 58 ]. Furthermore, the hunt for efficient immune checkpoint inhibitors and indicators to predict the efficacy of immunotherapy is critical.…”

Potential Mechanism of Colchicine against COVID-19 and Non-Small Cell Lung Cancer based on Network Pharmacology and Bioinformatics Analysis

“…Since the SARS-CoV-2 virus reduces the availability of ACE2 through ACE2 binding and entry, researchers believe that the RAS system and the imbalance of ACE1 and ACE2 activity (enhanced Ang II) play an important role in the stage of COVID-19 infection [78,79] . In studies related to NSCLC, we learned that TLR4 is a functional receptor for resistin migration and invasion in LUAD cells, promoting LUAD metastasis through TLR4/NF-κB related pathway [80,81] , TLR4 activation also protects the lung from inflammation during any underlying tumorigenesis [82] . Chemokine CCL2 can affect the development of lung cancer cell metastasis [83] , its knockdown or autophagy induction can successfully reverse drug resistance in tumor cells [84] , and may serve as potential predictors and therapeutic targets for survival in NSCLC patients [85] .…”