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Regulation of Heat Shock Proteins by miRNAs in human breast cancer. | LitMetric

Regulation of Heat Shock Proteins by miRNAs in human breast cancer.

Microrna

Department of Basic Pharmaceutical Sciences, Division of Biochemistry, Faculty of Pharmacy, Cumhuriyet University, Sivas, 58140, Turkey.

Published: July 2015

AI Article Synopsis

  • Cancer cells have faster metabolic rates than normal cells, leading to improper protein folding and a need for more Heat Shock Proteins (HSPs) to maintain protein function.
  • Pseudogenes and miRNAs are crucial in regulating tumor suppressors and oncogenes, with specific miRNAs showing both oncogenic and tumor-suppressive roles in breast cancer.
  • The CellMiner platform was used to analyze miRNAs linked to HSPs and pseudogenes in breast cancer cell lines, revealing significant correlations and suggesting potential new avenues for cancer research and understanding post-translational regulation mechanisms.

Article Abstract

Metabolic rates of cancer cells are faster compared to normal cells. This faster rate yields aberrant protein folding and causes loss of protein function. Therefore, cancer cells need more Heat Shock Proteins (HSPs) for proper substrate- protein folding on oncogenic pathways. Pseudogenes regulate tumor suppressors and oncogenes, and pseudogenes are deregulated in cancer progression. Further, alterations in miRNA expression have been identified in different cancer types. MiRNAs also have both oncogenic and tumour-suppressive roles in breast cancer post-transcriptional gene regulation. Breast cancer is a genetic disease and we performed miRNA analysis in human breast cancer cell lines to identify miRNAs in association with HSPs and pseudogenes by employing CellMiner; a web-based suite. CellMiner integrates several databases and help analysing microarray metadata. The experimental data provide a platform for researchers to compare macromolecules' relationships in NCI-60 cell lines. Breast cancer associated miRNAs gathered from literature and analyzed by employing this suite, significantly correlated HSP genes and pseudogenes in the breast cancer are determined as; HSPA13, HSP90AB1, TRAP1, HSPB1, DNAJB4, HSPD1 and HSP90AA4P, HSPB1P1, DNAJC8P1, HSPD1P9 respectively. HSPs involved in breast cancer are regulated by several miRNAs and miRNA regulators from CellMiner data found as hsa-miR-17, hsa-miR-22, hsa-miR-93, hsa-miR-106a, hsa-miR-125b, hsa-miR-130a, and hsamiR- 141. Cross check of the determined miRNAs and target HSPs was performed by target site prediction software. Comparison of the experimental data from CellMiner and software predicted data indicate differences. CellMiner data provide a vast miRNA types compared to prediction softwares-web tools data and reported miRNAs in the literature. Therefore, reported key miRNAs in this work that are not studied earlier may help cancer researchers to uncover novel posttranslational regulation mechanisms. Cancer cells use HSP network as an escape mechanism from apoptosis, therefore inhibition of associated HSPs by modulating miRNAs may provide a novel therapy for the tumorigenesis.

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Source
http://dx.doi.org/10.2174/2211536604666141216214140DOI Listing

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