The critical role and functional mechanism of microRNA-146a in doxorubicin-induced apoptosis in breast cancer cells.

BACKGROUND: Breast cancer among women is the most frequently diagnosed cancer and the leading cause of death worldwide. There many advances in diagnosing and treating this disease, early diagnosis and treatment are still a significant challenge in the early stages. In recent years, microRNAs have attracted much attention in cancer diagnosis and treatment. However, the role of miR-146a in breast cancer is still controversial. We aimed to investigate the roles of miR-146a in apoptosis in breast cancer cells. METHODS: A microarray dataset from the GEO database was selected, and using the GEO2R tool, the gene expression profile of this dataset was extracted. Then, the target scan database was used to explore the miR-146a target genes. The link between the signaling pathways was collected. We used miR-146a mimic, which was transfected to the MCF-7 cells to investigate the miR-146a roles in the apoptosis. The expression levels of miR-146a and BAX, BCL-2, and p-21(most essential genes in the apoptosis) were quantified by qPCR and western blot analysis. RESULTS: Our findings indicated that doxorubicin induces miR-146a expression. In addition, overexpression of miR-146a affected MCF-7 cell viability, induced apoptosis, and led to reduced expression levels of BCL-2 and P-21, as well as increased BAX expression levels. CONCLUSION: Considering the role of doxorubicin in inducing apoptosis and increasing the expression of miR-146a, it can be suggested that this miR is involved in inducing apoptosis in BC cells. In addition, miR-146a can be considered a therapeutic candidate.

Investigating the role of circulating tumor cells in gastric cancer: a comprehensive systematic review and meta-analysis.

Investigating the role of circulating tumor cells (CTCs) and their characteristics is still controversial in patients with gastric cancer (GC). Therefore, in this study, to provide a comprehensive review and meta-analyses of the literature on association of CTCs with gastric cancer, Scopus, Web of Science, Embase, and Medline were searched for systematic reviews and meta-analyses conducted during February 2022 using the keywords. Risk of bias, hazard ratios (HRs), and risk differences (RD) were assessed. Forty-five studies containing 3,342 GC patients from nine countries were assessed. The overall prevalence of CTC in GC was 69.37% (60.27, 77.78). The pooled result showed that increased mortality in GC patients was significantly associated with positive CTCs, poor overall survival (HR = 2.73, 95%CI 2.34-3.24, p < 0.001), and progression-free survival rate (HR = 2.78, 95%CI 2.01-3.85, p < 0.001). Subgroup analyses regarding markers, detection methods, treatment type, presence of distance metastasis, presence of lymph node metastasis, and overall risk of bias showed significant associations between the groups in terms of the incidence rates of CTCs, OS, and PFS. In addition, the results of risk differences based on sampling time showed that the use of the cell search method (RD: - 0.19, 95%CI (- 0.28, - 0.10), p < 0.001), epithelial marker (RD: - 0.12, 95%CI (- 0.25, 0.00), p 0.05) and mesenchymal markers (RD: - 0.35, 95%CI (- 0.57, - 0.13), p 0.002) before the treatment might have a higher diagnostic power to identify CTCs and also chemotherapy treatment (RD: - 0.17, 95%CI (- 0.31, - 0.03), p 0.016) could significantly reduce the number of CTCs after the treatment. We also found that the risk differences between the clinical early and advanced stages were not statistically significant (RD: - 0.10, 95%CI (- 0.23, 0.02), P 0.105). Also, in the Lauren classification, the incidence of CTC in the diffuse type (RD: - 0.19, 95%CI (- 0.37, - 0.01), P0.045) was higher than that in the intestinal type. Meta-regression analysis showed that baseline characteristics were not associated with the detection of CTCs in GC patients. According to our systematic review and meta-analysis, CTCs identification may be suggested as a diagnostic technique for gastric cancer screening, and the outcomes of CTC detection may also be utilized in the future to create personalized medicine programs.

Hsa_circITGA4/ miR-1468/EGFR/ PTEN a Master Regulators Axis in Glioblastoma Development and Progression.

In the fight against glioblastoma, circular RNA is emerging as a functional molecule. However, how circular RNA (circRNA) is regulated and what role it plays is still a mystery. In this research, different bioinformatics approaches were used to evaluate glioblastoma circRNA sequencing and array data, with the goal of developing a putative molecular sponge mechanism control network. The circRNAs were obtained from the Gene Expression Omnibus datasets. MicroRNA-circRNA interactions were predicted using CircInteractome. The microRNAs' expression and survival trends were screened using the TCGA database. MicroRNA gene targets were predicted using the MiRnet database. Sponge network gene candidates were screened using data from the GEPIA. The roles of the targeted genes were to be explained by analyzing data from Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. To build the network and display the outcomes, we utilized python program, and enrichment online Bioinformatics databases. The circRNAs hsa_circITGA4_002, hsa_circITGA4_001, hsa_circITGA4_003, hsa_circ_0030855, hsa_circ_0030857 were chosen from among GBM patients and control group. Upregulation of hsa-miR-1468, hsa-miR-3683, hsa-miR-1273c, and hsa-miR-4665-3p were associated with a poor prognosis in GBM. MicroRNA targets such as ITGA4, LAMA2, EGFR, PTEN, COL1A4, and NCAM2 were analyzed using expression and survival data. The Apoptosis, cell adhesion molecules, PI3K/AKT and P53 signaling pathways were the most abundant functional categories among gene targets. The circRNA molecular sponge regulatory network includes hsa-miR-1468 and hsa-miR-4665-3p. In this network, hs hsa_circITGA4_002, hsa_circITGA4_001, hsa_circ_0030857, EGFR, PTEN, and ITGA4 may represent GBM therapeutic targets. Their role in GBM needs additional study.

Association between the Expression Levels of MicroRNA-101, -103, and -29a with Autotaxin and Lysophosphatidic Acid Receptor 2 Expression in Gastric Cancer Patients.

Background: Gastric cancer (GC) is regarded as the most prevalent malignancy with the high mortality rate, worldwide. However, gastroscopy, a biopsy of suspected sample, and detecting CEA, CA19-9, and CA72-4 are presently used, but these diagnostic approaches have several limitations. Recently, microRNAs as the most important member of noncoding RNAs (ncRNAs) have received attention; recent evidence demonstrates that they can be used as the promising candidate biomarkers for GC diagnosis. We aimed to investigate the association between the microRNA-29a, -101, and -103 expression and autotaxin (ATX) and lysophosphatidic acid receptor 2 (LPA2) expression in GC patients. Material and Methods. The present study was conducted on 40 paired samples of primary GC tissue and adjacent noncancerous tissue. The gene expression levels of miR-101, -103, -29, ATX, and LPA2 were analyzed by quantitative reverse-transcription PCR (qRT-PCR). Besides, the protein levels of ATX and LPA2 were evaluated using western blot. Results: The expression levels of miR-29 and miR-101 were significantly lower (p value < 0.0001), but the miR-103 and LPA2 were significantly higher in gastric tumor samples compared to the corresponding nontumor tissues (p value < 0.0001). Moreover, the diagnostic accuracy of miRs to discrimine the GC patients from noncancerous controls was reliable (miR-101, sensitivity: 82.5% and specificity: 85%; miR-103, sensitivity: 72.5% and specificity: 90%; miR-29, sensitivity: 77.5% and specificity: 70%). Conclusion: It seems that determining the expression level of miR-101, -103, and -29, as the novel diagnostic biomarkers, has diagnostic value to distinguish GC patients from healthy individuals.

Molecular study of the proliferation process of beta cells derived from pluripotent stem cells.

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disorder, increasing in the number of patients and poses a severe threat to human health. Significant advances have been made in DM treatment; the most important of which is differentiation and proliferation of beta cells from IPSCs. METHODS: Data were collected from PUBMED at various time points up to the academic year of 2020. The related keywords are listed as follows: "Induced pluripotent stem cell", "Proliferation", "Growth factor", "Small molecule", "cardiotoxicity" and "Scaffold." RESULT: The use of growth factors along with small molecules can be a good strategy for beta-cell proliferation. Also, proliferation of beta cells on nanofibers scaffolds can create a similar in vivo environment, that leads to increased function of beta-cell. Some transcription factors that cause beta cells proliferation play an important role in inflammation; so, it is essential to monitor them to prevent inflammation. CONCLUSION: Finally, the simultaneous use of growth factors, micronutrients and scaffolds can be an excellent strategy to increase the proliferation and function of beta cells derived from IPSCs.

Evaluation of Important Molecular Pathways and Candidate Diagnostic Biomarkers of Noninvasive to Invasive Stages in Gastric Cancer by In Silico Analysis.

Gastric cancer affects millions of people each year; it is the fifth deadliest cancer globally. Due to failure to perform routine tests such as endoscopy, it is usually diagnosed in the invasive stages. Therefore, finding diagnostic biomarkers in blood can help to speed up the initial diagnosis of cancer. This study aimed to find appropriate diagnostic biomarkers in the extracellular matrix of noninvasive to invasive stages of gastric cancer patients, using bioinformatics analysis. First, we selected the appropriate datasets from the GEO database. We evaluated the genes' signaling pathways, biological processes, and molecular functions. More accurately, we assessed the genes, in which their protein products are released into the extracellular matrix; we evaluated their protein network. Then, we validated the candidate proteins in the GEPIA and TCGA databases. The extracellular matrix, tyrosine kinase receptors, and immune response pathways are effective factors, which are related to the highly expressed genes and metabolism; cell cycle pathways are also impressive on low-expression genes. 69 highly expressed proteins are released into the extracellular matrix. After drawing the protein network, 5 proteins were selected as more suitable candidates for further studies. These proteins' expression significantly increases in the human samples, and the survival chart showed up to about 80% mortality in the individuals over time. With integrated bioinformatics analysis, BGN, LOX, MMP-9, SERPINE1, and TGFB1 proteins have been selected as suitable diagnostic biomarkers for noninvasive to invasive stages of gastric cancer. Further studies are needed to evaluate more precise mechanisms between these proteins.

Effect of rosiglitazone on circulating malondialdehyde (MDA) level in diabetes based on a systematic review and meta-analysis of eight clinical trials.

Patients with type 2 diabetes have high levels of malondialdehyde (MDA), and clinical data suggest a reducing effect of rosiglitazone (RSG) on the level of MDA in these patients. However, the results of available studies on the level of MDA in RSG-treated patients are not univocal. This meta-analysis aimed to assess the impact of RSG on the level of MDA. We performed a comprehensive search of PubMed, the Institute for Scientific Information Web of Science, Embase, Scopus, and Cochrane Library for related controlled trials until July 2020. Eligible studies were selected based on the inclusion criteria. Extracted data from each study were combined using a random-effects model. Sensitivity and subgroup analyses were conducted to explore potential heterogeneity. Eight trials with 456 subjects met the inclusion criteria. The results significantly showed the reducing effect of RSG on circulating MDA level (-0.47 µmol/mL; 95% CI -0.93 to -0.01; p=0.04; I2=82.1%; p heterogeneity=0.00) in individuals with T2D. No publication bias was observed with Begg's rank correlation (p=0.71) and Egger's linear regression (p=0.52) tests. Subgroup analyses showed that an intervention dose of 8 mg/day in serum samples was found to have a reducing effect on the level of MDA (-0.56 µmol/mL; 95% CI -0.98 to -0.14; p=0.008; I2=11.4%; p heterogeneity=0.32). Random-effects meta-regression did not show any significant association between the level of MDA and potential confounders including RSG dose, treatment duration, and sex. In conclusion, we found a significant reduction in MDA concentration in subjects with T2D who received a dose of 8 mg of RSG daily.

Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers.

Gastric and esophageal cancers are as main cancers of the gastrointestinal (GI) tract, which are associated with poor diagnosis and survival. Several efforts were made in the past few decades to finding effective therapeutic approaches, but these approaches had several problems. Finding new biomarkers is a critical step in finding new approaches for the treatment of these cancers. Finding new biomarkers that cover various aspects of the diseases could provide a choice of suitable therapies and better monitoring of patients with these cancers. Among several biomarkers tissue specific and circulating microRNAs (miRNAs) have emerged as powerful candidates in the diagnosis of gastric and esophageal cancers. MiRNAs are small noncoding single-stranded RNA molecules that are found in the blood and regulate gene expression. These have numerous characteristics that make them suitable for being used as ideal biomarkers in cancer diagnosis. Research has indicated that the level and profile of miRNA in serum and plasma are very high. They are potentially noninvasive and sensitive enough to detect tumors in their primary stages of infection. Multiple lines of evidence indicate that the presence, absence, or deregulation of several circulating miRNAs (i.e., let-7a, miR-21, miR-93, miR-192a, miR-18a, and miR-10b for gastric cancer, and miR-21, miR-375, miR-25-3p, miR-151a-3p, and miR-100-3p for esophageal cancer) are associated with initiation and progression of gastric and esophageal cancers. The aim of this review is to highlight the recent advances in the roles of miRNAs in diagnosis and treatment of gastric and esophageal cancers.