Multi-Omics Analysis of the Prognostic and Immunological Role of Runt-Related Transcription Factor 3 in Pan-Cancer.

Runt-related transcription factor 3 (RUNX3) plays a pivotal role in tumor microenvironment and immune infiltration. However, the prognostic and immunological roles of RUNX3 in pancancer remain unclear. In the current study, we explored the expression profiles, prognostic landscape, and immune infiltration of RUNX3 in pancancer through a variety of online platforms, including HPA, ONCOMINE, UALCAN, GEPIA, PrognoScan, TCGA, TIMER, R2, and Reactome databases. In general, RUNX3 was widely expressed in tonsil, gallbladder, skin, spleen, lymph node, and bone marrow, and RUNX3 was frequently higher expression in tumor tissues compared to normal tissues. In prognostic analysis, the RUNX3 expression level was significantly correlated with the clinical outcomes of bladder cancer, blood cancer, brain cancer, breast cancer, colorectal cancer, lung cancer, and ovarian cancer. In mutation analysis, a total 72 mutation sites were located within amino acids 1 to 415 of RUNX3, including 65 missense sites and seven truncating sites, whereas the mutation frequency of skin cutaneous melanoma and uterine corpus endometrial carcinoma (UCEC) is relatively high (> 3%). In immune infiltration analysis, the RUNX3 expression level was significantly related to recognized markers and the immune infiltration levels of various types of immune cells in colon adenocarcinoma (COAD) and brain lower grade glioma (LGG). After that, 453 RUNX3 co-expressed genes were recognized in COAD, lymphoid neoplasm diffuse large B-cell lymphoma, LGG, and ovarian serous cystadenocarcinoma (OV). Pathway enrichment analysis revealed that RUNX3 co-expressed genes were remarkably enriched in immune system and tumor progression pathways. RUNX3 expression is associated with clinical prognosis, immune infiltration, and identified RUNX3 related pathways in a variety of tumors, which may serve as targets of promising prognostic markers and novel therapeutic targets for various human cancers.

The protective effect of gentisic acid on rheumatoid arthritis via the RAF/ERK signaling pathway.

BACKGROUND: RAF and ERK pathways are known to be activated in human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), which play an important role in the pathogenesis and destruction of RA. Gentisic acid (GA) was a natural product derived from plants, which has been reported can attenuate pressure overload-induced cardiac hypertrophy and fibrosis in mice through inhibition of the ERK1/2 pathway. Whether GA can inhibit the occurrence and development of RA through RAF/ERK signaling pathway has not been reported. The purpose of this study is to determine whether GA may have a certain therapeutic effect on RA-FLS. METHOD: Bovine type II collagen was used to establish a rat model of rheumatism. Enzyme-linked immunosorbent assay was used to detect inflammatory factors, anti-inflammatory mediators, and rheumatoid factor. Hematoxylin and eosin and TUNEL staining were used to detect the effect of GA on histochemical with rheumatoid arthritis. RAF, ERK, and p-ERK expressions in synovial tissue were measured by western blot and immunohistochemical. Besides, human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A was used to investigate the biological behavior influenced by GA. Apoptosis assay was performed to detect apoptosis of GA on MH7A cells. Transwell invasion assay was performed to detect the ability of cell migration. RESULT: The result showed that GA could reduce joint swelling and inflammation. At the same time, it can also promote the apoptosis of synovial cells and down-regulate the RAF/ERK pathway. CONCLUSION: GA may ameliorate inflammatory factors' abnormality, synovial hyperplasia, and apoptosis of synovium via inhibiting the RAF/ERK signaling pathway.