RESUMO
The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein-protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT-PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki-67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT-PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis.
RESUMO
Endometrial cancer (EC) is one of the most common gynecological cancers, and its risk factors include obesity and metabolic, genetic, and other factors. Recently, the circadian rhythm has also been shown to be associated with EC, as the severity of EC was found to be related to night work and rhythm disorders. Therefore, circadian rhythm disorders (CRDs) may be one of the metabolic diseases underlying EC. Changes in the circadian rhythm are regulated by clock genes (CGs), which in turn are regulated by non-coding RNAs (ncRNAs). More importantly, the mechanism of EC caused by ncRNA-mediated CRDs is gradually being unraveled. Here, we review existing studies and reports and explore the relationship between EC, CRDs, and ncRNAs.
RESUMO
Aim: Addressing both inflammation and epithelialization during the treatment of diabetic foot ulcers is an important step, but current treatment options are limited. MiRNA has important prospects in the treatment of diabetic foot refractory wound ulcers. Previous studies have reported that miR-185-5p reduces hepatic glycogen production and fasting blood glucose levels. We herein hypothesized that miR-185-5p might play an important role in the field of diabetic foot wounds. Materials and Methods: MiR-185-5p in skin tissue samples from patients with diabetic ulcers and diabetic rats were measured using quantitative real-time PCR (qRT-PCR). The streptozotocin-induced diabetes rat model (male Sprague-Dawley rats) for diabetic wound healing was conducted. The therapeutic potential was observed by subcutaneous injection of miR-185-5p mimic into diabetic rat wounds. The anti-inflammation roles of miR-185-5p on human dermal fibroblast cells were analyzed. Results: We found that miR-185-5p is significantly downregulated in diabetic skin (people with DFU and diabetic rats) compared to controls. Further, in vitro upregulation of miR-185-5p decreased the inflammatory factors (IL-6, TNF-α) and intercellular adhesion molecule 1 (ICAM-1) of human skin fibroblasts under advanced glycation end products (AGEs). Meanwhile, the increase of miR-185-5p promoted cell migration. Our results also confirmed that the topical increase of miR-185-5p decreases diabetic wound p-nuclear factor-κB (p-NF-κB), ICAM-1, IL-6, TNF-α, and CD68 expression in diabetic wounds. MiR-185-5p overexpression boosted re-epithelization and expedited wound closure of diabetic rats. Conclusion: MiR-185-5p accelerated wound healing of diabetic rats, reepithelization, and inhibited the inflammation of diabetic wounds in the healing process, a potentially new and valid treatment for refractory diabetic foot ulcers.
