CircZNF609 and circNFIX as possible regulators of glioblastoma pathogenesis via miR-145-5p/EGFR axis.

Glioblastoma is a rare and deadly malignancy with a low survival rate. Emerging evidence has shown that aberrantly expressed circular RNAs (circRNAs) play a critical role in the initiation and progression of GBM tumorigenesis. The oncogenic function of circZNF609 and circNFIX is involved in several types of cancer, but the role and underlying mechanism of these circRNAs in glioblastoma remain unclear. In this study, we hypothesized that circZNF609 and circNFIX may regulate EGFR through sponging miR-145-5p. Herein, we assessed the expression levels of circZNF609, circNFIX, miR-145-5p, and EGFR using quantitative polymerase chain reaction in glioblastoma patients and normal brain samples. The results showed that circZNF609, circNFIX, and EGFR expression levels were upregulated and miR145-5p was downregulated (p = 0.001, 0.06, 0.002, and 0.0065, respectively), while there was no significant association between clinicopathological features of the patients and the level of these genes expression. We also found a significant inverse correlation between miR145-5p and the expression of cZNF609, cNFIX and EGFR (p = 0.0003, 0.0006, and 0.009, respectively). These findings may open a new window for researchers to better understand the potential pathways involved in GBM pathogenesis. In conclusion, it may provide a new potential pathway for the development of effective drugs for the treatment of GBM patients.

Systematic review and meta-analysis of association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss: an update.

BACKGROUND: We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL. METHODS: A systematic search for studies that assessed the association between PAI-1 4G/5G polymorphism and RPL risk published in search sources, PubMed/Medline, ISI Web of Knowledge, Scopus, and Google Scholar till January 2024 was conducted. RESULTS: There were 23 case-control studies in total, with a high degree of statistical heterogeneity among them which indicated the need for subgroup analysis. We found a significant positive association between the risk of RPL and 4G/4G PAI-1 (OR: 2.57; 95% CI: 1.69-3.90), likewise 4G/5G (OR: 2/02 95% CI: 1.39-2.92) and mixed genotype (4G/4G+4G/5G) (OR: 2.31 95% CI: 1.81-2.93). Considering the ethnicity, the 4G/4G polymorphism is significantly associated with Asian descent (OR: 2.10; CI: 1.65-2.69) while the strong association (OR: 6.47; CI: 3.23-12.97) observed in the Greater Middle East descent is not statistically significant (P=0.16). PAI-1 4G/5G polymorphism association with RPL was only significant in Greater Middle East descent (OR: 2.93; CI: 2.41-3.56), and mixed genotype was significantly associated with RPL in Asian (OR: 2.37; CI: 1.55-3.61), Greater Middle East (OR: 3.01; CI: 2.16-4.19), and European populations (OR: 1.38; CI: 0.91-2.10). The association between RPL and PAI-1 4G/4G was significant for RPLs both under 12 weeks (OR: 1.82; 95% CI: 1.34-2.47), and under 24 weeks (OR: 1.46; 95% CI: 1.11-1.92), while considering heterozygote form the association was only significant for RPLs under 24 weeks (OR: 1.91; 95% CI: 1.58-2.31). Regarding the mixed genotype, there is a significant positive association between PAI-1 and RPL for RPLs under 12 weeks (OR: 2.09; 95% CI: 1.49-2.93), and under 24 weeks (OR: 2.10; 95% CI: 1.52-2.92). CONCLUSIONS: Our findings indicate a significant association between the rs1799762 PAI-1 polymorphism and the risk of RPL.

Increased Expression of MiR-27a and MiR-24-2 in Esophageal Squamous Cell Carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is one of the predominant types of esophageal cancer with poor prognosis which shows high prevalence in eastern countries. Studying microRNAs that were considered for their capabilities such as tissue-specific expression and involvement in different cell features may be informative in the field of diagnostic and prognostic tumor markers. The expression levels of miR-27a and miR-24-2 have been reported to be dysregulated in various cancers and contribute in tumorigenesis and progression; thus, evaluating their expressional behavior and its association with tumor states alteration in ESCC could potentially be helpful. METHODS: The study was conducted on 30 fresh specimens including tumor and normal counterparts' tissues of ESCC. After the extraction of total RNA, complementary DNA synthesis was performed by the use of linear specific primers. Eventually, real-time polymerase chain reaction was carried out for the measurement of microRNAs expression level. RESULTS: According to the obtained data, miR 27a and miR-24-2 were significantly upregulated (~2.5 fold, p < 0.05) in tumor specimens compared with their normal adjacent tissue; Moreover, upregulation of miR-27a and 24-2 showed cooperative relationship while analyzed. However, there was no correlation between clinicopathological features and microRNAs upregulation. CONCLUSIONS: The results of this study show that miR-27a and miR-24-2 cooperatively upregulate in ESCC and suggest that these microRNAs can be introduced as a candidate for further study in the field of screening and prognostic biomarkers.

Heat-induced inflammation and its role in esophageal cancer.

Esophageal cancer, the sixth most common cause of death from cancer worldwide, consists of different histological types and displays various patterns of incidence. Esophageal adenocarcinoma and esophageal squamous cell carcinoma are the most prevalent types. As epidemiological studies report that ingesting hot substances is one major risk factor for squamous cell carcinoma, evaluating the effect of this external stress on esophagus cells seems desirable. This specific kind of stress brings about cellular changes and stabilizes them by affecting different cellular features such as genetic stability, membrane integrity and the regulation of signaling pathways. It also causes tissue injury by affecting the extracellular matrix and cell viability. Thus, one of the main consequences of thermal injury is the activation of the immune system, which can result in chronic inflammation. The genetic alteration that has occurred during thermal injury and the consequent reduction in the function of repair systems is further strengthened by chronic inflammation, thereby increasing the probability that mutated cell lines may appear. The molecules that present in this circumstance, such as heat shock proteins, cytokines, chemokines and other inflammatory factors, affect intercellular signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells, signal transducer activator of transcription-3 and hypoxia-inducible factor 1α in supporting the survival and emergence of mutant phenotypes and the consequent malignant progression in altered cell lines. This investigation of these effective factors and their probable role in the tumorigenic path may improve current understanding.