hsa-miR-497 as a modulator of the expression in the presence or absence of chrna5 in breast cancer
Author(s)
Advisor
Konu Karakayalı, ÖzlenDate
2017-06Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
CHRNA5 is an important ligand-gated receptor with roles in addiction and in cancer. In
lung cancer, CHRNA5 dysregulation is well known. There is also expression of CHRNA5
in breast cancer cell lines. microRNAs regulate mRNA expression; and different
regulatory microRNAs are involved in different cancer types. microRNAs are thus
potential biomarkers to diagnose the diseases (e.g. cancer). However, there is no study
testing interactions between microRNAs and CHRNA5 in breast cancer. In the present
study, mir-497 was found to be one of the most downregulated microRNAs with testable
expression levels upon analysis of expression in the breast cancer cell line MCF7 when
exposed to CHRNA5 siRNA. RT-qPCR was performed to test the expression level of
mir-497. Validated target genes of mir-497 were found to be significantly related to a list
of different KEGG pathways significantly (p value < 0.001) among which there were P53
and PI3K-Akt signalling pathways.
Mimic-mir-497 treatment, alone or together with CHRNA5 siRNA, was applied on
MCF7 cells to understand the interaction between the miRNA and siRNA under
investigation. Selected target genes of mir-497 were tested; the most significantly
modulated genes were involved in P53 pathway. The results indicated interactions
between mir-497 and CHRNA5 however selected targets were not affected by mimicmir-
497.
GSE41079 and GSE41074 public datasets containing mRNA and microRNA expression
profiles of liver cancer cells treated with mimic-mir-497. Treatment were used to identify novel targets of mir-497 for future use. Immune system was detected in the second place
upon REACTOME analysis of GSE41079 and GSE41074. Using multiple online
microRNA-mRNA network tools mir-497 mRNA-miRNA networks were extracted for
all or only immune genes. The results from network based analyses helped identify
additional targets for later use in our mimic-siRNA system.