• Knockdown Singleminded-2s expression by shRNA and its impact on the progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) in breast cancer; An In-Silico study
  • Majdedin Ghalavand,1 Samira Mohammadi Yeganeh,2,* Ruhollah Dorostkar,3 Azar Moradi,4 Seyed Mahmoud Hashemi,5
    1. 1. Student Research Committee, Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Department of Biotechnology, School of Advanced Technology in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    2. 2. Department of Biotechnology, School of Advanced Technology in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    3. 4. Applied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
    4. 1. Student Research Committee, Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Department of Biotechnology, School of Advanced Technology in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    5. 5. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran


  • Introduction: Single-minded homolog 2 is a protein that in humans is encoded by the SIM2 gene. There are two known isoforms of SIM2 which play different roles in various tissues. The isoform SIM2 Short (SIM2s) has been shown to be specifically expressed in mammary gland tissue. SIM2s is a splice variant which lacks exon 11 of SIM2. It has been researched that SIM2s acts in mammary gland development and has tumor suppressive characteristics specifically in breast cancer. In a mouse specimen, when SIM2s was not expressed in mammary epithelial cells there were development defects leading to cancer-like characteristics in the cells. The defects were increased cell proliferation, cellular invasion of local stroma, loss of cellular polarity, and loss of E-cadherin cellular adhesion molecules. Observations suggest that SIM2s is essential for proper mammary gland development. Experiments reintroducing SIM2s in human breast cancer cells allowed for the tumor-suppressive characteristics to be observed. In this study, we survey genes that are involved in the pathway followed by Knocking down Singleminded-2s expression.
  • Methods: In expression datasets of NCBI (Gene Expression Omnibus), GSE44187 was selected. Data analyzed with GEO2R; distribution of value was checked graphically as a box plot. Most important Genes by P.Value imported in Enrichr Database. Finally, the analysis was done and important parts of Biological Process, Cellular Component, Molecular Function, and Jensen DISEASE identified.
  • Results: Enriched data in Enrichr online database showed that negative regulation of cell adhesion mediated by integrin (GO: 0033629) by BP, AIM2 inflammasome complex (GO:0097169) by CC, cadherin binding involved in cell-cell adhesion (GO:0098641) by MF and Lynch_syndrome/ Breast_disease(Score:468.88) by Jensen DISEASE; are calculated by combined score. Then in KEGG 2019 Human; showed Ether lipid metabolism / Estrogen signaling pathway / Hippo signaling pathway, are main pathways. In article results comparing normal human breast cells to human breast cancer cells with immunohistochemical staining showed that SIM2s was expressed more in the normal than the cancerous. Reintroducing SIM2s expression in breast cancer cells showed a decrease in growth, proliferation, and invasiveness.
  • Conclusion: In Silico analysis of common genes and pathways reveal SIM2s represses the actions of matrix metalloprotease-3 gene (MMP3) which include cell migration, cancer progression, and epithelial to mesenchymal transitions (EMT). SIM2s also represses the SLUG transcription factor which in turn suppresses EMT. It is also could be found that SIM2s decrease glycolytic enzyme activity and promotes oxidative phosphorylation in breast cancer and then, coupled with increased autophagy and ROS, inhibit tumor growth and metastasis.
  • Keywords: Singleminded-2s, Breast Cancer, In-Silico study