Association of the Sp1 binding site and -1997 promoter variations in COL1A1 with osteoporosis risk: The application of meta-analysis and bioinformatics approaches offers a new perspective for future research.

As a complex disease, osteoporosis is influenced by several genetic markers. Many studies have examined the link between the Sp1 binding site +1245 G > T (rs1800012) and -1997 G > T (rs1107946) variations in the COL1A1 gene with osteoporosis risk. However, the findings of these studies have been contradictory; therefore, we performed a meta-analysis to aggregate additional information and obtain increased statistical power to more efficiently estimate this correlation. A meta-analysis was conducted with studies published between 1991-2020 that were identified by a systematic electronic search of the Scopus and Clarivate Analytics databases. Studies with bone mineral density (BMD) data and complete genotypes of the single-nucleotide variations (SNVs) for the overall and postmenopausal female population were included in this meta-analysis and analyzed using the R metaphor package. A relationship between rs1800012 and significantly decreased BMD values at the lumbar spine and femoral neck was found in individuals carrying the "ss" versus the "SS" genotype in the overall population according to a random effects model (p < 0.0001). Similar results were also found in the postmenopausal female population (p = 0.003 and 0.0002, respectively). Such findings might be an indication of increased osteoporosis risk in both studied groups in individuals with the "ss" genotype. Although no association was identified between the -1997 G > T and low BMD in the overall population, those individuals with the "GT" genotype showed a higher level of BMD than those with "GG" in the subgroup analysis (p = 0.007). To determine which transcription factor (TF) might bind to the -1997 G > T in COL1A1, 45 TFs were identified based on bioinformatics predictions. According to the GSE35958 microarray dataset, 16 of 45 TFs showed differential expression profiles in osteoporotic human mesenchymal stem cells relative to normal samples from elderly donors. By identifying candidate TFs for the -1997 G > T site, our study offers a new perspective for future research.

miR-16 enhances miR-302/367-induced reprogramming and tumor suppression in breast cancer cells.

Overexpression of either miR-302 or miR-302/367 cluster induces reprogramming of cancer cells and exerts tumor-suppressive effects by induction of mesenchymal-to-epithelial transition, apoptosis and a less proliferative capacity. Several reports have described miR-16 as a tumor suppressor microRNA (miRNA). Here, we studied the impact of exogenous induction of miR-16 in MDA-MB-231 and SK-BR-3 breast cancer cells following overexpression of miR-302/367 cluster and investigated whether transfection of these cells by a mature miR-16 mimic could affect the reprogramming state of the cells and their tumorigenicity. miR-16 enhanced the expression levels of OCT4A, SOX2, and NANOG, generally known as transcription or pluripotency factors, and suppressed proliferation and invasiveness of these cells. Meanwhile, inhibition of miR-16 counteracted both the reprogramming effect and the antitumor function of miR-302/367 in the breast cancer cells. Current results indicate that miR-16 can work as an adjuvant to improve both cancer cell reprogramming and tumor-suppressive function of miR-302/367 cluster in MDA-MB-231 and SK-BR-3 cells, while its inhibition counteracts all of these effects. Combined application of miRNAs that share some common targets in cancer cell signaling pathways may provide new approaches for repression of multiple hallmarks of cancer.

Repression of TGF-ß Signaling in Breast Cancer Cells by miR-302/367 Cluster.

OBJECTIVE: Epigenetic alterations of the malignantly transformed cells have increasingly been regarded as an important event in the carcinogenic development. Induction of some miRNAs such as miR-302/367 cluster has been shown to induce reprogramming of breast cancer cells and exert a tumor suppressive role by induction of mesenchymal to epithelial transition, apoptosis and a lower proliferation rate. Here, we aimed to investigate the impact of miR-302/367 overexpression on transforming growth factor-beta (TGF-ß) signaling and how this may contribute to tumor suppressive effects of miR-302/367 cluster. MATERIALS AND METHODS: In this experimental study, MDA-MB-231 and SK-BR-3 breast cancer cells were cultured and transfected with miR-302/367 expressing lentivector. The impact of miR-302/367 overexpression on several mediators of TGF-ß signaling and cell cycle was assessed by quantitative real-time polymerase chain reaction (qPCR) and flow cytometry. RESULTS: Ectopic expression of miR-302/367 cluster downregulated expression of some downstream elements of TGF-ß pathway in MDA-MB-231 and SK-BR-3 breast cancer cell lines. Overexpression of miR-302/367 cluster inhibited proliferation of the breast cancer cells by suppressing the S-phase of cell cycle which was in accordance with inhibition of TGF-ß pathway. CONCLUSION: TGF-ß signaling is one of the key pathways in tumor progression and a general suppression of TGF-ß mediators by the pleiotropically acting miR-302/367 cluster may be one of the important reasons for its anti-tumor effects in breast cancer cells.

Analysis of microRNA and Gene Expression Profiles in Alzheimer's Disease: A Meta-Analysis Approach.

Understanding the molecular mechanisms underlying Alzheimer's disease (AD) is necessary for the diagnosis and treatment of this neurodegenerative disorder. It is therefore important to detect the most important genes and miRNAs, which are associated with molecular events, and studying their interactions for recognition of AD mechanisms. Here we focus on the genes and miRNAs expression profile, which we have detected the miRNA target genes involved in AD. These are the most quintessential to find the most important miRNA, to target genes and their important pathways. A total of 179 differentially expressed miRNAs (DEmiRs) and 1404 differentially expressed genes (DEGs) were obtained from a comprehensive meta-analysis. Also, regions specific genes with their molecular function in AD have been demonstrated. We then focused on miRNAs which regulated most genes in AD, alongside we analyzed their pathways. The miRNA-30a-5p and miRNA-335 elicited a major function in AD after analyzing the regulatory network, we showed they were the most regulatory miRNAs in the AD. In conclusion, we demonstrated the most important genes, miRNAs, miRNA-mRNA interactions and their related pathways in AD using Bioinformatics methods. Accordingly, our defined genes and miRNAs could be used for future molecular studies in the context of AD.