ABSTRACT
Cancer cachexia is a complex metabolic syndrome characterized by muscle wasting, fat decomposition, unplanned weight loss, anorexia and immune dysfunction. Cachexia can significantly reduce the efficacy of antitumor therapies and increase treatment-related toxicity on cancer patients. It increases the symptom burden in patients, affects the quality of their life, ultimately shortens patients' survival. Lucubrating the pathogenesis of cachexia is of great significance to provide rationale treatment guidance. Here we reviewed the research progress on pathogenesis of cancer cachexia, including inflammatory response mediated by TNF-α, IL-1, IL-6 and STAT-3 and abnormal nutrition metabolism, as well as mitochondrial dysfunction.
ABSTRACT
Objectives: Circular RNA Homeodomain Interacting Protein Kinase 3 (circHIPK3) is one of the most researched circRNAs in recent 5 years. Many individual studies confirmed that aberrantly expression of circHIPK3 held prognostic value in various tumors. Thus, the aim of this meta-analysis is to assess its prognostic potentials and functions in malignant tumors. Materials and methods: Multiple databases were carefully searched for articles published about circHIPK3 over the past 10 years. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to demonstrate prognostic value of circHIPK3 using Stata 15.0 software. Results: 8 studies including 1175 patients were ultimately enrolled in this meta-analysis. Pooled results showed that abnormal expression of circHIPK3 was significantly correlated with unfavorable OS (pooled HR=2.12, 95% CI: 1.69-2.66) and DFS/PFS (HR=2.28, 95% CI: 1.67-3.10) in cancer patients. Additionally, abnormal expression of circHIPK3 was also related to the distal metastasis of the tumors (OR: 3.27, 95%CI: 2.16-4.97, p<0.001). Conclusions: Abnormal expression of circHIPK3, no matter high or low expression, was associated with poor clinical outcomes in multiple cancer types. More comprehensive studies were required to verify and strengthen the clinical value of circHIPK3 in human malignant diseases.
ABSTRACT
Macrophages are essential inflammatory cells which regulate the features of immune reactions within tumors. Many studies have reported their regulatory roles in immunity through cytokines and cell signaling. However, relatively few studies have focused on their metabolic features and mechanisms. We aimed to determine the signaling pathway regulating cell metabolism and the mechanism related to the regulation of human tumor-associated macrophages (TAMs) in gastric cancer (GC). Tumor-infiltrated macrophages were isolated from human GC tissues using magnetic beads, gene transcription was determined by real-time PCR, protein expression was monitored using western blots, metabolites were determined using HPLC, and transcriptional regulation was analyzed by the luciferase-based reporter gene system. A significant decrease in microRNA (miR)-30c and an increase in regulated in development and DNA damage responses 1 (REDD1) were detected in human GC TAMs, the transcription of miR-30c was negatively correlated with REDD1. MicroRNA-30c expression was suppressed by hypoxia-inducible factor-1α activation and related to decreased mTOR activity as well as glycolysis in human GC TAMs. Hypoxia-regulated miR-30c downregulated REDD-1 expression by targeting its 3'UTR. Overexpression of miR-30c or restored mTOR activity in macrophages with miR-30cLow expression promoted M1 macrophage differentiation and function in TAMs. Therefore, hypoxia in the human GC microenvironment suppressed the expression of miR-30c, and decreased mTOR activity as well as glycolysis in GC TAMs, thus inhibiting M1 differentiation and function. These results provide a novel metabolic strategy for tumor microenvironment-based therapy.
