IDH1 regulates the expression of interferon pathway-related gene IFIT3

Abstract

Abstract: Objective To explore the role of IDH1 in the expression of RNA binding proteins (RBPs) in glioma cell line LN229. Methods Lentivirus was used to construct IDH1 knockdown and control cells, and the expression of IDH1 was validated by RT-qPCR (real-time quantitative PCR) and Western blot. Then the total RNA of cells from each group was extracted for RNA sequencing (RNA-seq); the differentially expressed genes (DEGs) were identified by limma package and enriched pathways were analyzed; the differentially expressed RBPs were selected according to the RBP database and protein-protein interaction network was constructed by string database; finally, the expression level of candidate RBPs was tested in IDH1 knockdown, over-expressed and mutant cells(R132H) respectively. Results A total of 259 DEGs were detected in IDH1 knockdown LN229 cells, including 146 upregulated and 113 downregulated genes. These DEGs were significantly enriched in interferon related pathways and included 14 RBP-encoding genes, 9 of which were significantly enriched in interferon related pathways and showed close interaction; compared with the control group, IDH1 knockdown in LN229 significantly upregulated the expression of all the nine RBPs (P＜0.001), and IDH1 overexpression only downregulated IFIT3 (P＜0.01) involving in interferon pathway, while IDH1 mutation had no significant effect on IFIT3. Conclusions IDH1 regulates expression of interferon pathway related gene IFIT3 in LN229 cells.

Key words: glioma, IDH1, interferon pathway, IFIT3

CLC Number:

TANG Wan-jun, PENG Xiao-zhong, HAN Wei. IDH1 regulates the expression of interferon pathway-related gene IFIT3[J]. Basic & Clinical Medicine, 2021, 41(7): 988-994.

References

[1]Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of tumors of the central nervous system: a summary[J]. Acta Neuropathol, 2016, 131:803-820.
[2]Olar A, Wani KM, Alfaro-Munoz KD, et al. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas[J]. Acta Neuropathol, 2015, 129:585-596.
[3]Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas[J]. N Engl J Med, 2009, 360:765-773.
[4]Lunde BM, Moore C, Varani G, et al. RNA-binding proteins: modular design for efficient function[J]. Nat Rev Mol Cell Biol, 2007, 8:479-490.
[5]Brinegar AE, Cooper TA. Roles for RNA-binding proteins in development and disease[J]. Brain Res, 2016, 1647:1-8.
[6]Wang ZX, Tang WJ, Yuan JG, et al. Integrated analysis of RNA-binding proteins in glioma[J]. Cancers, 2020, 12: 892. doi: 10.3390/cancers12040892.
[7]Calvert AE, Chalastanis A, Wu Y, et al. Cancer-associa-ted IDH1 promotes growth and resistance to targeted therapies in the absence of mutation[J]. Cell Rep, 2017, 19:1858-1873.
[8]Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate[J]. Nature, 2009, 462:739-744.
[9]Yang Z, Liang H, Zhou Q, et al. Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms[J]. Cell Res, 2012, 22:1328-1338.
[10]Pidugu VK, Pidugu HB, Wu MM, et al. Emerging functions of human IFIT proteins in cancer[J]. Front Mol Biosci, 2019, 6:148. doi: 10.3389/fmolb.2019.00148.
[11]Zhang JF, Chen Y, Lin GS, et al. High IFIT1 expression predicts improved clinical outcome, and IFIT1 along with MGMT more accurately predicts prognosis in newly diagnosed glioblastoma[J]. Hum Pathol, 2016, 52:136-144.
[12]Lai KC, Chang KW, Liu CJ, et al. IFN-induced protein with tetratricopeptide repeats 2 inhibits migration activity and increases survival of oral squamous cell carcinoma[J]. Mol Cancer Res, 2008, 6:1431-1439.
[13]Shu X, Dong Li, Hai QZ, et al. RIG-G as a key mediator of the antiproliferative activity of interferon-related pathways through enhancing p21 and p27 proteins[J]. Proc Natl Acad Sci, 2006, 103:16448-16453.
[14]Lo UG, Pong RC, Yang D, et al. IFNgamma-induced IFIT5 promotes epithelial-to-mesenchymal transition in prostate cancer via miRNA processing[J]. Cancer Res, 2019, 79:1098-1112.

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