MiR‐192‐5p/RB1/NF‐κBp65 signaling axis promotes IL‐10 secretion during gastric cancer EMT to induce Treg cell differentiation in the tumour microenvironment

Abstract

Background Regulatory T (Treg) cells are important components of the tumour microenvironment (TME) that play roles in gastric cancer (GC) metastasis. Although tumour cells that undergo epithelial‐mesenchymal transition (EMT) regulate Treg cell function, their regulatory mechanism in GC remains unclear. Methods The miR‐192‐5p was identified by examining three Gene Expression Omnibus GC miRNA expression datasets. RNA immunoprecipitation (RIP) and dual‐luciferase reporter assays were conducted to identify interactions between miR‐192‐5p and RB1. The role of miR‐192‐5p/RB1 in GC progression was evaluated based on EdU incorporation, wound healing and Transwell assays. An in vitro co‐culture assay was performed to measure the effect of miR‐192‐5p/RB1 on Treg cell differentiation. In vivo experiments were conducted to explore the role of miR‐192‐5p in GC progression and Treg cell differentiation. Results MiR‐192‐5p was overexpressed in tumour and was associated with poor prognosis in GC. MiR‐192‐5p bound to the RB1 3′‐untranslated region, resulting in GC EMT, proliferation, migration and invasion. MiR‐192‐5p/RB1 mediated interleukin‐10 (IL‐10) secretion by regulating nuclear factor‐kappaBp65 (NF‐κBp65), affecting Treg cell differentiation. NF‐κBp65, in turn, promoted miR‐192‐5p expression and formed a positive feedback loop. Furthermore, in vivo experiments confirmed that miR‐192‐5p/RB1 promotes GC growth and Treg cell differentiation. Conclusion Collectively, our studies indicate that miR‐192‐5p/RB1 promotes EMT of tumour cells, and the miR‐192‐5p/RB1/NF‐κBp65 signaling axis induces Treg cell differentiation by regulating IL‐10 secretion in GC. Our results suggest that targeting miR‐192‐5p/RB1/NF‐κBp65 /IL‐10 may pave the way for the development of new immune treatments for GC.

Improving the prediction for the response to radiotherapy of clinical tumor samples by using combinatorial model of MicroRNA expression

“…Previous studies reported that miR192 regulated the EMT pathway ( Khella et al, 2013 ). Song et al confirmed that miR‐192 promoted EMT of gastric cancer, migration and invasion by targeting RB1 ( Song et al, 2022 ). In additional, the previous study has demonstrated that miR-192 was significantly upregulated in cisplatin-resistant lung cancer cells, and miR-192 induced cisplatin resistance through activating the NF-κB pathway ( Li et al, 2022 ).…”

Decoding the potential role of regulatory T cells in sepsis‐induced immunosuppression

“…In a cohort of 106 burn patients (who are prone to burn sepsis), increased levels of IL-10 expressed by Tregs are related to poorer clinical outcomes and prognosis [31]. Meanwhile, IL-10 can promote the differentiation of Tregs [32]. Apoptosis and pyroptosis of immune cells are master factors in the development of lymphopenia.…”

Clinical application and detection techniques of liquid biopsy in gastric cancer

“…They are widely present in body fluids such as plasma, serum, and tumor patients’ exocytosis. Moreover, increasing studies have shown that circulating ncRNAs in the blood of tumor patients can be detected in large quantities and used as biomarkers for GC [ 169 , 170 ]. Our previous studies have shown that circPTPN22, which is up-regulated in GC plasma, can effectively differentiate GC patients from healthy controls; its AUC value can reach 0.857.…”