Hereditas最新文献

Background: In terms of global incidence and mortality, breast cancer continues to surpass all other cancers affecting women.

Methods: To explore the role of miR-596, qRT-PCR was applied to measure its expression in tissue and cell samples from 137 enrolled subjects. The regulatory interaction between miR-596 and EIF5AL1 was verified by dual-luciferase reporter assays. CCK-8 and Transwell assays were utilized to respectively measure the proliferation, migration, and invasion capabilities of the two breast cancer cell lines, MCF-7 and MDA-MB-231.

Results: A significant downregulation of miR-596 was observed in breast cancer tissues and cell lines (all P < 0.001). Clinically, reduced miR-596 expression was associated with advanced TNM stage, lymph node metastasis, and inferior overall survival (P < 0.05). EIF5AL1 was validated as a direct target gene of miR-596, and their expression levels were inversely correlated in clinical samples (r = -0.801, P < 0.001). Reintroduction of miR-596 markedly suppressed the proliferation, migration, and invasion of cancer cells, effects that were largely reversed by overexpressing EIF5AL1 (all P < 0.001).

Conclusion: In breast cancer, miR-596 suppresses malignancy and predicts prognosis by targeting EIF5AL1. Thus, therapeutic modulation of this axis offers novel avenues for treatment and risk assessment.

Background: Dysregulated expression of long non-coding RNA (lncRNA) TUG1 participates in the etiopathogenesis of polycystic ovary syndrome (PCOS). This study analyzed the genetic association of the TUG1 rs5749201 polymorphism in PCOS patients.

Methods: Genotype and allele distributions of rs5749201 were analyzed in 210 PCOS patients and 230 healthy volunteers. Serum TUG1 levels were detected via qRT-PCR. The relationship between gene polymorphism and PCOS risk was analyzed via multivariate logistic regression.

Results: Compared with the control group, the PCOS group had a significantly higher proportion of carriers with TUG1 rs5749201 AA genotype and a lower proportion of TT genotype carriers. Rs5749201 TT genotype carriers had notably reduced PCOS risk. This genetic association was also found in dominant and recessive models, with the locus independently linked to PCOS (OR = 0.427, 95%CI: 0.242-0.753; P = 0.003). AA genotype carriers had higher LDL, TG and FBS than AT/TT genotype carriers. PCOS patients had elevated TUG1 levels, with AA genotype carriers showing the highest.

Conclusion: TUG1 rs5749201 was linked to PCOS susceptibility, which is correlated with its regulatory role in TUG1 expression.

Background: Luoshi Neiyi prescription (LSNYP) is a traditional Chinese medicine that has a clinical effect on endometriosis (EMs). This study combined network pharmacology with experimental validation to explore its potential molecular mechanisms.

Methods: The primary components of LSNYP were identified based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). The possible target proteins were predicted using the SwissTargetPrediction online tool. The GeneCards and DisGeNET databases were used to identify targets associated with EMs. The protein-protein interaction (PPI) network, herb-component-target network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Molecular docking, molecular dynamics (MD) simulation and experimental verification were carried out.

Results: 217 potential therapeutic targets were identified. Enrichment analyses revealed involvement in key biological processes and pathways, including cell migration, inflammatory response, focal adhesion, and the VEGF signaling pathway, which are closely related to the adhesion-invasion-angiogenesis progression in EMs pathogenesis. Molecular docking and MD simulation results showed stable binding between corresponding components and typical targets (ICAM1, MMP9 and VEGFA) involved in the progression. Experimental results demonstrated that LSNYP could decrease typical targets of the progression in rats and inhibit the invasion, migration and adhesion capabilities of human endometriotic stromal cells (ESCs).

Conclusion: These findings suggest LSNYP may be a promising candidate for EMs, potentially through inhibiting the adhesion-invasion-angiogenesis progression.

Background: Epiphycan (EPYC) has been confirmed to play an oncogenic role in many cancers. However, its role and mechanism in gastric cancer (GC) progression has not been explored.

Methods: The levels of EPYC and NOP2/Sun domain 2 (NSUN2) were detected by qRT-PCR and western blot. Cell proliferation, apoptosis, migration and invasion were determined by cell counting kit 8 assay, colony formation assay, flow cytometry, wound healing assay and transwell assay. Fe²⁺ and iron levels were examined to assess cell ferroptosis. Actinomycin D assay was used to detect the effect of NSUN2 knockdown on EPYC mRNA stability, and methylated RNA immunoprecipitation (MeRIP) assay was performed to determine the effect of NSUN2 silencing on 5-methylcytosine (m5C) level of EPYC. Xenograft tumors were constructed to explore the regulation of NSUN2 knockdown on GC tumorigenesis in vivo.

Results: EPYC was abnormally higher expressed in GC tissues and cells. Knockdown of EPYC restrained GC cell proliferation, migration and invasion, while enhanced apoptosis and ferroptosis. NSUN2 had elevated expression in GC, which could increase the mRNA stability and expression of EPYC through m5C modification. NSUN2 silencing inhibited GC cell proliferation, metastasis, promoted apoptosis and ferroptosis, while these effects were reversed by EPYC overexpression. In vivo experiments revealed that NSUN2 downregulation reduced GC tumorigenesis by decreasing EPYC level in vivo.

Conclusion: NSUN2-mediated m5C modification of EPYC contributed to GC cell growth and metastasis, which provided a novel regulatory axis for understanding the pathogenesis of GC.