STIM and ORAI genes, interactions with transcription factors, differential gene expression and co-expression analysis on breast invasive carcinoma dataset
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1
Universiti Teknologi MARA Puncak Alam, Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, 42300 Bandar Puncak Alam,, Malaysia
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2
Center for Bioinformatics, Saarland University, Building E2 1, P.O. Box 151150, 66041, Germany
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3
University of Rostock Medical Center, Institute for Biostatistics and Informatics in Medicine and Ageing Research (IBIMA), Ernst-Heydemann-Straße 8, 18057, Germany
Background
Store-operated calcium (Ca2+) entry (SOCE) is ubiquitous mechanism for Ca2+ entry in eukaryotic cells, which regulates diverse cellular functions. SOCE is achieved primarily by the gating of the plasma membrane (PM)-localized-channel, ORAI, by the ER-localized Ca2+-sensing protein, STIM. The discovery of transcription factor binding site (TFBS) motifs in specific locations on the STIM and ORAI promoters remains elusive. Moreover, the knowledge of the defects of STIM and ORAI genes expression and/or function linked to disease such as breast cancer is still obscured.
Methods
Here, the HOCOMOCO and EPDnew databases were used to obtain a set of position weight matrix (PWM) and promoter sequences of STIM and ORAI, respectively, and mapped the possible binding motif proteins using the FIMO tool. The results were then mapped with the set of transcription factors (TFs) targeting STIM and ORAI gene which were retrieved from the CheA database.
Results
Ten predictive interactions were used between transcription factors bound to promoter regions of STIM and ORAI genes based on predictions using the STRING, prePPI, and mentha databases. Then, the collection of 63 TFs was used as gene of interest for co-expression and differential expression analysis on breast invasive carcinoma (BRCA) dataset. There, ORAI genes were found to be up-regulated, in contrast with STIM1 and STIM2 which were down-regulated.
Conclusion
Unveiling the predicted transcription factors bound to the promoter regions of STIM and ORAI genes, the regulations of these genes and differential networks properties may suggest putative interactions for experimental studies and allows us to gain knowledge in relation to breast cancer.
Keywords:
STIM,
Orai,
Breast invasive carcinoma (BRCA),
promoters,
Transcription Factors
Conference:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019.
Presentation Type:
Oral Presentation
Topic:
Cancer
Citation:
Mohamed
R,
Sethi
R,
Hamed
M and
Helms
V
(2019). STIM and ORAI genes, interactions with transcription factors, differential gene expression and co-expression analysis on breast invasive carcinoma dataset.
Front. Pharmacol.
Conference Abstract:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”.
doi: 10.3389/conf.fphar.2019.63.00040
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Received:
18 Oct 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Dr. Ruzianisra Mohamed, Universiti Teknologi MARA Puncak Alam, Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, 42300 Bandar Puncak Alam,, Selangor, Malaysia, ruzianisra@puncakalam.uitm.edu.my