Title:Regulation of Heat Shock Proteins by miRNAs in Human Breast Cancer
Volume: 3
Issue: 2
Author(s): Aykut Ozgur, Lutfi Tutar and Yusuf Tutar
Affiliation:
Keywords:
Cancer, heat shock protein, miRNA, protein folding, pseudogene.
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.
