Bioinformatic Analysis of miR-200b/429 and Hub Gene Network in Cervical Cancer.

The miR-200b/429 located at 1p36 is a highly conserved miRNA cluster emerging as a critical regulator of cervical cancer. Using publicly available miRNA expression data from TCGA and GEO followed by independent validation, we aimed to identify the association between miR-200b/429 expression and cervical cancer. miR-200b/429 cluster was significantly overexpressed in cancer samples compared to normal samples. miR-200b/429 expression did not correlate with patient survival; however, its overexpression correlated with histological type. Protein-protein interaction analysis of 90 target genes of miR-200b/429 identified EZH2, FLT1, IGF2, IRS1, JUN, KDR, SOX2, MYB, ZEB1, and TIMP2 as the top ten hub genes. PI3K-AKT and MAPK signaling pathways emerged as major target pathways of miR-200b/429 and their hub genes. Kaplan-Meier survival analysis showed the expression of seven miR-200b/429 target genes (EZH2, FLT1, IGF2, IRS1, JUN, SOX2, and TIMP2) to influence the overall survival of patients. The miR-200a-3p and miR-200b-5p could help predict cervical cancer with metastatic potential. The cancer hallmark enrichment analysis showed hub genes to promote growth, sustained proliferation, resistance to apoptosis, induction of angiogenesis, activation of invasion, and metastasis, enabling replicative immortality, evading immune destruction, and tumor-promoting inflammation. The drug-gene interaction analysis identified 182 potential drugs to interact with 27 target genes of miR-200b/429 with paclitaxel, doxorubicin, dabrafenib, bortezomib, docetaxel, ABT-199, eribulin, vorinostat, etoposide, and mitoxantrone emerging as the top ten best candidate drugs. Taken together, miR-200b/429 and associated hub genes can be helpful for prognostic application and clinical management of cervical cancer.

Integrated bioinformatic analysis to understand the association between phthalate exposure and breast cancer progression.

Phthalates have been extensively used as plasticizers while manufacturing plastic-based consumer products. Estradiol mimicking properties and association studies suggest phthalates may contribute to breast cancer (BC). We performed an in-silico analysis and functional studies to understand the association between phthalate exposure and BC progression. Search for phthalate-responsive genes using the comparative toxicogenomics database identified 20 genes as commonly altered in response to multiple phthalates exposure. Of the 20 genes, 12 were significantly differentially expressed between normal and BC samples. In BC samples, 9 out of 20 genes showed a negative correlation between promoter methylation and its expression. AHR, BAX, BCL2, CAT, ESR2, IL6, and PTGS2 expression differed significantly between metastatic and non-metastatic BC samples. Gene set enrichment analysis identified metabolism, ATP-binding cassette transporters, insulin signaling, and type II diabetes as highly enriched pathways. The diagnostic assessment based on 20 genes expression suggested a sensitivity and a specificity >0.91. The aberrantly expressed phthalate interactive gene influenced the overall survival of BC patients. Drug-gene interaction analysis identified 14 genes and 523 candidate drugs, including 19 BC treatment-approved drugs. Di(2-ethylhexyl) phthlate (DEHP) exposure increased the growth, proliferation, and migration of MCF-7 and MDA-MB-231 cells in-vitro. DEHP exposure induced morphological changes, actin cytoskeletal remodeling, increased ROS content, reduced basal level lipid peroxidation, and induced epithelial to mesenchymal transition (EMT). The present approach can help to explore the potentially damaging effects of environmental agents on cancer risk and understand the underlined pathways and molecular mechanisms.

Small nucleolar RNA and its potential role in breast cancer - A comprehensive review.

Small Nucleolar RNAs (snoRNAs) are known for their canonical functions, including ribosome biogenesis and RNA modification. snoRNAs act as endogenous sponges that regulate miRNA expression. Thus, precise snoRNA expression is critical for fine-tuning miRNA expression. snoRNAs processed into miRNA-like sequences play a crucial role in regulating the expression of protein-coding genes similar to that of miRNAs. Recent studies have linked snoRNA deregulation to breast cancer (BC). Inappropriate snoRNA expression contributes to BC pathology by facilitating breast cells to acquire cancer hallmarks. Since snoRNAs show significant differential expression in normal and cancer conditions, measuring snoRNA levels could be useful for BC prognosis and diagnosis. The present article provides a comprehensive overview of the role of snoRNAs in breast cancer pathology. More specifically, we have discussed the regulation, biological function, signaling pathways, and clinical utility of abnormally expressed snoRNAs in BC. Besides, we have also discussed the role of snoRNA host genes in breast tumorigenesis and emerging and future research directions in the field of snoRNA and cancer.

The emerging role of miRNA clusters in breast cancer progression.

Micro RNAs (miRNAs) are small non-coding RNAs that are essential for regulation of gene expression of the target genes. Large number of miRNAs are organized into defined units known as miRNA clusters (MCs). The MCs consist of two or more than two miRNA encoding genes driven by a single promoter, transcribed together in the same orientation, that are not separated from each other by a transcription unit. Aberrant miRNA clusters expression is reported in breast cancer (BC), exhibiting both pro-tumorogenic and anti-tumorigenic role. Altered MCs expression facilitates to breast carcinogenesis by promoting the breast cells to acquire the various hallmarks of the cancer. Since miRNA clusters contain multiple miRNA encoding genes, targeting cluster may be more attractive than targeting individual miRNAs. Besides targeting dysregulated miRNA clusters in BC, studies have focused on the mechanism of action, and its contribution to the progression of the BC. The present review provides a comprehensive overview of dysregulated miRNA clusters and its role in the acquisition of cancer hallmarks in BC. More specifically, we have presented the regulation, differential expression, classification, targets, mechanism of action, and signaling pathways of miRNA clusters in BC. Additionally, we have also discussed the potential utility of the miRNA cluster as a diagnostic and prognostic indicator in BC.