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Transcriptional Regulation of CYP2D6 by Nrf2 and Its Implications in Breast Cancer Therapy: Bioinformatics and Experimental Evidence Ferbian Milas Siswanto; Maria Dara Novi Handayani; Lonah Lonah; Rita Dewi; Zita Arieselia; Linawati Hananta; Putu Suwarastra Andarisuta
The Indonesian Biomedical Journal Vol 17, No 1 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i1.3194

Abstract

BACKGROUND: Tamoxifen (TAM) resistance in patient with breast cancer is the leading cause of mortality among women globally. Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of TAM, and recently NF-E2-related factor 2 (Nrf2) has recently been found as its regulator. However, the impact of Nrf2-mediated CYP2D6 regulation in the context of breast cancer and TAM resistance are currently unknown. Therefore, this study was conducted to examine the role of CYP2D6 and Nrf2 in breast cancer prognosis. MEDTHODS: The roles of CYP2D6 and Nrf2 were investigated in the T47D breast cancer cell line and T47D-derived TAM-resistant cells by examining the gene expression, cell viability, and transcriptional regulation by quantitative reverse transcription polymerase chain reaction (qRT-PCR), MTT, and reporter gene assay, respectively. Additionally, comprehensive in silico analysis of the transcriptomic and clinical data from The Cancer Genome Atlas database were performed to uncover the prognostic role of CYP2D6 and its regulator in breast cancer patients. RESULTS: CYP2D6 mRNA was low and Nrf2 protein was high in TAM-resistant T47D cells compared to parental cells. Nrf2 knockdown upregulated CYP2D6 mRNA levels and enhanced the cytotoxicity of TAM. Similarly, in silico analysis revealed that low CYP2D6 mRNA and high Nrf2 protein were related to a lower probability of survival. The rs1238662089 within the identified Nrf2-binding site was found to greatly affect CYP2D6 expression levels, indicating its role as predictor for better prognosis. CONCLUSION: This study revealed for the first time that Nrf2 regulates CYP2D6expression in breast cancer and is involved in TAM sensitivity; thus, plays a role in breast cancer patient prognosis.KEYWORDS: breast cancer, CYP2D6, Nrf2, pharmacoepigenetics, SNPs
In Silico Analysis of miRNA in Type 2 Diabetes Mellitus and Colorectal Cancer: Molecular Connections and Biomarker Potential Alexander Ryan Wihardja; Ana Lucia Ekowati; Milas Siswanto, Ferbian
Journal of Urban Health Research Vol. 4 No. 2 (2026): Journal of Urban Health Research
Publisher : School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.25170/juhr.v4i2.7497

Abstract

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia caused by insulin resistance and impaired insulin secretion, affecting 537 million adults worldwide in 2021 and projected to reach 783 million by 2045. T2DM increases the risk of malignancies, particularly colorectal cancer (CRC). MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have emerged as molecular links between T2DM and CRC through their roles in proliferation, apoptosis, metabolism, and insulin signaling. Shared pathways, including PI3K/AKT/mTOR and IGF-1 signaling, support common pathogenic mechanisms. Due to their stability and disease-specific expression, miRNAs represent promising biomarkers. This study employs an in silico bioinformatics approach to identify shared dysregulated miRNAs, predict their target genes, analyze relevant molecular pathways, and evaluate their regulatory roles connecting T2DM with CRC development. Methods: This study employed an in silico approach using miRNA expression data from GEO datasets (GSE262614, GSE185845, GSE115513, GSE156732), analyzed with R under the criteria |Log2FC| > 1 and p < 0.05. Differentially expressed miRNAs from each dataset were compared using a Venn diagram to identify consistently dysregulated miRNAs. Target gene prediction was conducted using miRTargetLink 2.0 and miRWalk, followed by validation with mRNA datasets GSE25724 and GSE44076. Pathway enrichment analyses were performed using GO and KEGG through ShinyGO and Enrichr Results:  Analysis revealed that hsa-miR-182-3p was the only miRNA consistently experiencing upregulation in both T2DM and colorectal cancer. From hsa miR-182-3p a total of 9 validated target genes were identified, and most of them are involved in MAPK, mTOR, cell cycle, and insulin signaling pathways which are key pathways implicated in both diseases. Conclusion: This study indicates that hsa-miR-182-3p may serve as a molecular mediator linking the pathophysiological mechanisms of T2DM, such as insulin resistance and hyperinsulinemia, with colorectal cancer tumorigenesis, and may hold potential as a biomarker.
Genetic Variation Analysis of FSHB Gene Exon 3 in Goats (Capra hircus) Using in Silico Restriction Fragment Length Polymorphism (RFLP) Hendro Sukoco; Hermilinda Parera; Victor Lenda; Nancy Diana Foeh; Dihan Kurnia; Dwi Nurhayati; Muhammad Mirandy Pratama Sirat; Ratna Ermawati; Made Bagus Erlangga; Salmin -; Annisa Putri Cahyani; Ferbian Milas Siswanto
JURNAL KAJIAN VETERINER Vol 14 No 1 (2026): Jurnal Kajian Veteriner
Publisher : FAKULTAS KEDOKTERAN HEWAN UNIVERSITAS NUSA CENDANA

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.35508/jkv.v14i1.25855

Abstract

Studi ini bertujuan untuk melakukan analisis in silico awal Restriction Fragment Length Polymorphism (RFLP) pada ekson 3 gen Hormon Perangsang Folikel Beta (FSHB) pada kambing (Capra hircus) menggunakan enzim restriksi BspMAI dan PstI. Empat sekuens ekson 3 gen FSHB yang telah dipublikasikan, masing-masing sepanjang 310 bp, diperoleh dari basis data NCBI dan dianalisis dengan digesti restriksi virtual. Hasil analisis memprediksi dua pola restriksi pada sekuens yang dianalisis: pola tidak terpotong sepanjang 310 bp dan pola terpotong yang menghasilkan fragmen sepanjang 200 bp dan 110 bp. Pola tidak terpotong sepanjang 310 bp ditemukan pada tiga sekuens, sedangkan pola 200 bp dan 110 bp ditemukan pada satu sekuens. Hasil ini menunjukkan kemungkinan adanya perbedaan situs restriksi pada atau di sekitar situs pengenalan BspMAI/PstI pada ekson 3 gen FSHB kambing. Namun, karena penelitian ini terbatas pada analisis komputasional sekuens publik dan tidak melibatkan sampel biologis, amplifikasi PCR, pengurutan, pencernaan enzim restriksi langsung, atau validasi elektroforesis, temuan ini masih bersifat pendahuluan. Penelitian lebih lanjut menggunakan penyelarasan sekuens berganda, identifikasi SNP, dan validasi PCR-RFLP laboratorium pada populasi kambing sebenarnya diperlukan untuk mengkonfirmasi potensi penggunaan BspMAI/PstI dalam studi genetika kambing
Co-Authors A.A. Ayu Putri Permatasari Adrianto, Nicholas Agustina Agustina Akbarrizki , Muzizat Alexander Ryan Wihardja Ana Lucia Ekowati Ana Lucia Ekowati Anak Agung Ayu Mirah Adi Andanawari , Suci Annisa Putri Cahyani Annisa Putri Cahyani Annisa Putri Cahyani Bambang Hadi Kartiko Boedi Prihatini Yenniastoeti Cahyani, Annisa Putri Chela Krisna Denata Dahniar Dahniar Daniel Ardian Soeselo Deka Uli Fahrodi Dewa Ayu Widia Kusuma Ningrat, Dewa Ayu Widia Kusuma Dewi, Ni Putu Eny Sulistya Dihan Kurnia DK, Taufik Dwi Nurhayati DWI SURYANTO Erwin Adams Pangkahila Fatqur Rochman Finnegan, Meisy Haeryl Nur Asrar Heidy Heidy Hendro Sukoco Hermilinda Parera I Dewa Gde Tara Damayanthi, I Dewa Gde Tara I Gede Widhiantara I Gede Widhiantara I Gusti Agung Ayu Suartini I Gusti M. Aman I Gusti Made Aman I Made Kardena I Nyoman Suarsana I Wayan Putu Sutirta Yasa I Wayan Rosiana I Wayan Suryawan Irma Susanti S Irma Susanti S J. A. Pangkahila Linawati Hananta, Linawati Linoh, Steven Lucky Lonah, Lonah Made Bagus Erlangga Maria Dara Novi Handayani, Maria Dara Novi Marsudi Marsudi Marsudi Marsudi Melita Hidajat Mufassir, Mufassir muhammad irfan Muhammad Irfan Muhammad Mirandy Pratama Sirat Muzizat Akbarrizki, Muzizat Nancy Diana Foeh Ni Putu Eny Sulistya Dewi Ni Putu Vidia Tiara Timur Novelya , Novelya Nur Hanifah Septiani, Nur Hanifah Nur Saidah Said Pakpahan, Hotmaria Agustina Pamella Haryanto Permatasari, Anak Agung Ayu Putri Priyatun, Rumi Putu Dede Yudi Utama, Putu Dede Yudi Putu Suwarastra Andarisuta Ratna Ermawati Risha Catra Pradhany Rita Dewi Rita Dewi Dewi Rosa Zulfikhar Rustang Rustang Salmin Salmin - Salmin Dengo Siti Nuraliah Sri Utami Sri Wahyuni Suci Andanawari Suhartina Suhartina Sukoco, Hendro Suriansyah, Suriansyah Surya, Junita Elvira Panji Taufan Hendra Wirawan Tri Adi Putra, Tri Adi Victor Lenda Wibowo, Haris Tri Wijaya, Ferdian Manuel William William Zita Arieselia Zulfikhar, Rosa