Background: Ferroptosis has garnered increasing attention; however, relevant researches are insufficient.

Methods: We incorporated two microarray datasets from Gene Expression Omnibus (GEO) and utilized the FerrDb website to identify ferroptosis genes. Differential expression analysis of ferroptosis-related genes and functional enrichment analysis were performed using R software. Machine learning technique was employed to screen for core genes and evaluate their correlation with immune cells, ultimately identifying core genes with diagnostic value. In vivo and in vitro experiments were conducted to confirm the relationship between the core gene and ulcerative colitis (UC) ferroptosis. We conducted a UC mouse model using 3% dextran sodium sulfate (DSS) free drinking water method. We detected the expression of Fatty Acid Biding Protein-4 (Fabp4), glutathione peroxidase 4 (Gpx4), ferritin heavy chain (Fth), protein kinase B (PKB, also named as Akt), Phosphatidylinositide 3-kinases (Pi3k), and interleukin-1β (IL-1β) in the mouse colon through quantitative real-time PCR (qPCR) and western blot (WB) analysis. Additionally, we performed an in vitro experiment using the THP-1 cell line. The cells were pretreated with Ferrostatin-1 (Fer-1) and FABP4 inhibitor (BMS 3094033) for 1 hour, followed by the addition of Erastin. We then measured the intracellular expression of FABP4, GPX4, FTH, AKT, PI3K, and IL-1β using qPCR and immunofluorescence.

Results: FABP4 is a crucial gene in ulcerative colitis (UC). It is associated with the infiltration of immune cells like macrophages, dendritic cells, and neutrophils, as well as Phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway. In vivo experiments have demonstrated that the expressions of Fabp4, Fth, Pi3k, Akt, and Il-1β were elevated in the colon of UC mice, while the Gpx4 was reduced. In vitro experiments found that after adding FABP4 inhibitors, the expressions of FTH, PI3K, AKT, and IL-1β decreased, while GPX4 increased.

Conclusions: FABP4 has been identified as a pivotal gene in the ferroptosis process in UC. It is suggested that FABP4 regulates the PI3K/AKT signaling pathway, thereby playing a crucial role in UC's ferroptosis development.

Background: Preeclampsia (PE) is a major health complication for pregnant women that increases the risk of mortality and morbidity. Knowledge of the complex molecular mechanisms associated with PE is incomplete and methods for early diagnosis and treatment options in PE are limited. MicroRNAs (miRNAs) are short non-coding RNAs involved in pathogenesis of various diseases including PE. In our previous studies, we identified a relationship between miR-510-3p and PE. However, the exact molecular mechanisms and genes regulated by miR-510-3p have not been elucidated.

Methods: In this study, we employed the bioinformatic tools including miRbase, RNAcomposer, RNAfold, TargetScan, miRDB, miRTarbase to analyze the secondary structure and targets of miR-510-3p from the publicly available databases. We compared the miR-510-3p target genes with PE genes retrieved from the NCBI (National Center for Biotechnology Information) genes database. The miR-510-3p target genes that were involved in PE were further subjected to gene ontology (GO) and Kyoto Encyclopaedia for Genes and Genomes (KEGG) pathway analysis to analyse their biological, molecular and cellular role in PE. STRING, Shiny GO, Cytoscape and Metascape were used for the GO and KEGG analysis.

Results and Conclusions: MicroRNA-510-3p had a minimum free energy of –29.10 Kcal and A+U content of 55.4%, suggesting stability and binding affinity towards its targets. Genes that were involved in the positive regulation of angiogenesis were identified, since angiogenesis is an important process in PE. ADAM12, ANGPT2, CHRNA7, DDAH1, ERAP1, FGF2, GRN, HGF, HIF1A, HK2, HMGB1, HMOX1, IL1A, KDR, NRP1, PRKCB, SERPINE1, SIRT1, TGFBR2, THBS1, TLR3, VEGFA, and WNT5A were the miR-510-3p targets involved in the positive regulation of angiogenesis. In conclusion, miR-510-3p is postulated to play an important role in the pathogenesis of PE. Hence, further studies could define miR-510-3p as a novel therapeutic target for PE.

Background: Poly (ADP-ribose) polymerase (PARP) 1 and PARP2 deficiency in the uterus results in the loss of pregnancy. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), a PARP1 binding nucleus-localized long non-coding ribonucleic acid (RNA), is downregulated in patients with recurrent pregnancy loss (RPL). However, the correlation between MALAT1 and PARPs, and their roles in RPL remain unclear.

Methods: In this study, MALAT1, PARP1, and PARP2 levels were examined in the decidua from a cohort consisting of 35 patients with RPL and 15 healthy controls. The interaction between MALAT1 and PARP2 was identified in primary decidual stromal cells using a ribonucleoprotein immunoprecipitation assay and confirmed by RNA pull-down and immunofluorescence. Deoxyribonucleic acid (DNA) damage, cell viability, and apoptosis were examined by immunoblotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and flow cytometry in PARP2 knockdown cells.

Results: MALAT1 and PARP2 levels were downregulated in patients with RPL. The messenger RNA level of PARP2 was positively correlated with MALAT1 levels (r = 0.41, p = 0.013). PARP2 bound MALAT1 close to the 3′ end and colocalizes with it in the cell nucleus. In PARP2 knockdown cells, MALAT1 was re-localized to the nucleus rim and cytoplasm and degraded more quickly. In decidual stromal cells, PARP2 knockdown led to DNA damage, decreased cell viability, and increased apoptosis.

Conclusions: We identified the interaction between PARP2 and MALAT1 for the first time and constructed a correlation between MALAT1/PARP2 dysregulation and the occurrence of RPL, which provides new clues for RPL treatment.

Background: Studies have shown that foam cell formation and cholesterol leakage are important causes of abdominal aortic aneurysm (AAA), long non-coding RNA (lncRNA) antisense non-coding RNA at the INK4 locus (ANRIL) is a biomarker for diagnosing AAA, and ATP-binding cassette transporter A1 (ABCA1) is involved in cholesterol transport. However, the mechanism of action of ABCA1 and ANRIL in AAA is unclear. This work mainly explored the effect of the RR, RK and KK genotypes of the R219K locus of the ABCA1 and ANRIL on the occurrence and development of AAA.

Methods: In this study, quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of ABCA1 and ANRIL in AAA and normal tissues. Eukaryotic expression vectors (RR, RK, KK) of the ABCA1 allele were introduced into vascular smooth muscle cells (VSMCs) or human monocytic leukemia cells (THP). Oil red O staining was used to detect the foam cell formation rate after THP-1 treated with oxidized low-density lipoprotein (oxLDL), and a kit was used to detect the intracellular lipid content. An enzyme-linked immunosorbent assay (ELISA) was used to detect apolipoprotein A-I (apoA-Ⅰ), high-density lipoprotein-C (HDL-C), IL-6 (interleukin-6) and TNF-α (tumor necrosis factor-α). Western blotting was used to detect MMP-2 (matrix metallo proteinase-2) and MMP-9. In addition, VSMCs were treated with angiotensin II (Ang II). The mitogen activity of VSMCs was detected by 5-ethynyl-2′-deoxyuridine (EdU) staining, and the cycle distribution and apoptosis of VSMCs were assessed by flow cytometry. Cell scratch and transwell were used to detect migration of VSMCs, and Western blotting was used to detect the expression of apoptosis-related proteins (Bcl-2 (B-cell lymphoma-2), Bax (Bcl-2 Associated X protein) and Caspase 3).

Results: In AAA, ABCA1 levels were downregulated, and ANRIL were upregulated (p < 0.001). Foam cell formation and a reduction in intracellular lipid content are induced by transfection with pc-ABCA1-KK, which promotes the outflow of cholesterol from THP-1 macrophages. pc-ABCA1-KK promoted expression of apoA-Ⅰ and HDL-C while inhibiting inflammation and matrix degradation (p < 0.01). Similarly, transfection of pc-ABCA1-KK promoted cell proliferation in VSMCs (p < 0.05). However, transfection with pc-ABCA1-RK and pc-ABCA1-RR did not yield any effects. The ABCA1-KK allele can affect cholesterol metabolism in THP-1 cells and alter the biological behavior of VSMCs by inhibiting ANRIL.

Conclusion: The ABCA1-KK allele affects the development of AAA by regulating ANRIL to modulate cholesterol metabolism in THP-1 cells and alter the biological behavior of VSMCs.

Background: Emerging evidence has indicated that microRNAs (miRNAs) play a significant role in multiple biological processes, including controlling the cell cycle, apoptosis, autophagy, and metabolic reprogramming. Among them, microRNA (miRNA)-518a-3p has been revealed to display a notably key function during the development of many cancer types, including colorectal cancer, breast cancer, and squamous cell carcinoma. However, its functions and molecular mechanisms during hepatocellular carcinoma (HCC) progression remain unclear. In this study, we aim to elucidate the specific biological processes and mechanisms of miRNA-518a-3p affecting HCC, so as to provide reference for finding new therapeutic targets.

Methods: Molecular and cell biology experiments were used to demonstrate the biological functions and molecular mechanisms of miRNA-518a-3p in HCC. Quantitative reverse transcription PCR (RT-qPCR) detected the miRNA-518a-3p expression level in HCC tumor tissues, and its related prognostic effects were also investigated. Furthermore, its functions during HCC progression were investigated by Cell Counting Kit-8 (CCK-8) experiment, transwell assay in two HCC cell lines. Moreover, its potential mechanisms were analyzed by bioinformatic analysis, RT-qPCR, western blotting, a luciferase reporter assay, and rescue experiments.

Results: Downregulation of miRNA-518a-3p was found in HCC tumor tissues and correlated with an awful overall survival. Gain and loss of function analyses displayed miRNA-518a-3p repressed HCC cells proliferation, migration, and invasion. Bioinformatic analysis and luciferase reporter assays have shown that Zinc finger protein 281 (ZNF281), upregulated in HCC tumor tissues, was negatively regulated by miRNA-518a-3p. Moreover, rescue experiments demonstrated that the suppression of HCC progression by miRNA-518a-3p was mediated by ZNF281.

Conclusions: Our study indicated that miRNA-518a-3p inhibited hepatocarcinogenesis by suppressing ZNF281 expression, indicating that miRNA-518a-3p is a promising therapeutic approach targeting the treatment of HCC.