Insulin receptor substrate 1 gene expression is strongly up-regulated by HSPB8 silencing in U87 glioma cells
Author:
Hnatiuk Oksana S.1, Tsymbal Dariia O.1, Minchenko Dmytro O.12, Khita Olena O.1, Viletska Yulia M.1, Rundytska Olha V.1, Kozynkevych Halyna E.2, Maslak Hanna S.3, Minchenko Oleksandr H.1
Affiliation:
1. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine , Kyiv , Ukraine 2. National Bohomolets Medical University , Kyiv , Ukraine 3. Dnipropetrovsk State Medical Academy , Dnipro , Ukraine
Abstract
Abstract
Objective. The aim of the present investigation was to study the expression of genes encoding IRS1 (insulin receptor substrate 1) and some other functionally active proteins in U87 glioma cells under silencing of polyfunctional chaperone HSPB8 for evaluation of the possible significance of this protein in intergenic interactions.
Methods. Silencing of HSPB8 mRNA was introduced by HSPB8 specific siRNA. The expression level of HSPB8, IRS1, HK2, GLO1, HOMER3, MYL9, NAMPT, PER2, PERP, GADD45A, and DEK genes was studied in U87 glioma cells by quantitative polymerase chain reaction.
Results. It was shown that silencing of HSPB8 mRNA by specific to HSPB8 siRNA led to a strong down-regulation of this mRNA and significant modification of the expression of IRS1 and many other genes in glioma cells: strong up-regulated of HOMER3, GLO1, and PERP and down-regulated of MYL9, NAMPT, PER2, GADD45A, and DEK gene expressions. At the same time, no significant changes were detected in the expression of HK2 gene in glioma cells treated by siRNA, specific to HSPB8. Moreover, the silencing of HSPB8 mRNA enhanced the glioma cells proliferation rate.
Conclusions. Results of this investigation demonstrated that silencing of HSPB8 mRNA affected the expression of IRS1 gene as well as many other genes encoding tumor growth related proteins. It is possible that the dysregulation of most of the studied genes in glioma cells after silencing of HSPB8 is reflected by a complex of intergenic interactions and that this polyfunctional chaperone is an important factor for the stability of genome function and regulatory mechanisms contributing to the tumorigenesis control.
Publisher
Walter de Gruyter GmbH
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism
Reference65 articles.
1. Abdel-Nour M, Carneiro LAM, Downey J, Tsalikis J, Outlioua A, Prescott D, Da Costa LS, Hovingh ES, Farahvash A, Gaudet RG, Molinaro R, van Dalen R, Lau CCY, Azimi FC, Escalante NK, Trotman-Grant A, Lee JE, Gray-Owen SD, Divangahi M, Chen JJ, Philpott DJ, Arnoult D, Girardin SE. The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling. Science 365, eaaw4144, 2019.10.1126/science.aaw4144 2. Abu Aboud O, Chen CH, Senapedis W, Baloglu E, Argueta C, Weiss RH. Dual and specific inhibition of NAMPT and PAK4 by KPT-9274 decreases kidney cancer growth. Mol Cancer Ther 15, 2119–2129, 2016.10.1158/1535-7163.MCT-16-0197 3. Acunzo J, Katsogiannou M, Rocchi P. Small heat shock proteins HSP27 (HspB1), αB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death. Int J Biochem Cell Biol 44, 1622–1631, 2012.10.1016/j.biocel.2012.04.002 4. Alaee M, Khaghani S, Behroozfar K, Hesari Z, Ghorbanhosseini SS, Nourbakhsh M. Inhibition of nicotinamide phosphoribosyltransferase induces apoptosis in estrogen receptor-positive MCF-7 breast cancer cells. J Breast Cancer 20, 20–26, 2017.10.4048/jbc.2017.20.1.20 5. Awais R, Spiller DG, White MR, Paraoan L. p63 is required beside p53 for PERP-Emediated apoptosis in uveal melanoma. Br J Cancer 115, 983–992, 2016.10.1038/bjc.2016.269
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