THEME: "Experimental Challenges in Studies of Drug Discovery, Development and Lead Optimization"
Islamic Azad University Najafabad, Iran
Title: Bioinformatics study of the role of important miRNAs and their mutations as a predicted drug target for inhibiting the FGFR2 dependent type of breast cancer
Negar
Balmeh, Department of Cell and Molecular Biology, School of Biology, Nour
Danesh Institution of Higher Education, Meymeh, Iran.
Introduction: Breast cancer is one of the most common causes of death in women.
The fibroblast growth factor(FGFR) protein plays a key role in the progression
and development of breast cancer cells and FGFR2 is a receptor of this protein.
Unfortunately, there is no definitive cure for breast cancer, and the methods
used to treat each have their own side effects. One of the new and increasing
therapies is the use of miRNAs because they can control and regulate the
expression of different genes.
Methods: By using TCGA datas, miRNAs related to breast cancer
tissues were gained. The sequences of 1550 miRNAs and FGFR2 were obtained
through the miRBase and NCBI, respectively. miRNAs and FGFR2 were docked by
RNAhybrid-BiBiServ2. MiRNASNPv3 was used to identify mutations in the seed sequence
of miRNAs with high affinity to 3’UTR of FGFR2 mRNA. Finally, the signaling
pathways inhibited by selected miRNAs was obtained using the DIANA(mirPath)
database.
Results: According to the results, five miRNAs had a high affinity to 3’UTR
of FGFR2 mRNA, and hsa-miR-6756-5p had the greatest inhibitory effect on FGFR2
in breast cancer by disruption of the Ras signaling pathway followed by
decreased tumor cell proliferation. Mutations, including rs1008291553,
rs985008481, rs769725887, rs2296320, rs72728267, rs1356532849, rs759820006,
rs1311227571, rs920134626, rs1326990805 in miRNAs reduced their affinity to
FGFR2.
Conclusion: The results of this survey showed that the mentioned miRNAs and SNPs
may be associated with controlling the progression and malignancy of breast
cancer. This study is bioinformatics and more experimental investigations need
to be applied to verify these results.