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Regulation of Survivin Gene Expression in Stem Cell and Cancer Stem Cells and Emphasis Approach Nihayah, Silviatun; Wanandi, Septelia Inawati
Indonesian Journal of Cancer Vol 19, No 1 (2025): March
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v19i1.1142

Abstract

Background: Gene expression regulation is a method that cells utilize to enhance or decrease the output of specific genes (proteins or RNA). In biological and medical research such as cancer, gene expression is routinely observed. Survivin is a protein that is commonly produced in cancer cells and has the potential to be investigated. Survivin is a unique protein with two distinct roles: preventing apoptosis and regulating cell division. The inhibitory apoptosis protein (IAP) family includes the smallest member. Furthermore, Survivin is highly expressed in a variety of somatic stem cell types as well as human embryonic stem cells. Comparing most cancer cells to normal tissues, survivin is also present in higher amounts. This review aimed to examine the properties of survivin, how it is expressed in cancerous and normal stem cells, how it affects proliferation or apoptosis, and how to block their expression. Methods: The literature on the regulation of survivin expression in cancer cells and stem cells that was published in English between 2014 and 2024 is reviewed in this study. For articles, we looked through PubMed, Scopus, and the Google Scholar database. In order to support the theories, publications from before 2014 were also tracked down.Results: Molecular mechanism studies indicate that survivin participates in numerous signaling pathways, including MAPK, STAT3, b-catenin, Wnt, Notch, and others, and also controls the progression of the cell cycle and cytokinesis. Several elements, such as signaling pathway blockage siRNA technology, and CRISPR/Cas9 system have been discovered to aid in the induction of cancer cell death. Conclusion: Survivin is linked to several cancer survival-related pathways, contributing to carcinogenesis. Its expression is associated with treatment resistance, tumor development, and poor prognosis.
Roles of the Survivin BIR Domain in Cellular Apoptosis and Proliferation: An In Silico Study Nihayah, Silviatun; Wanandi, Septelia Inawati; Erlina, Linda; Syahrani, Resda Akhra
Makara Journal of Science
Publisher : UI Scholars Hub

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Abstract

Survivin is an antiapoptotic protein that is highly expressed in cancer cells. We investigated the dual roles of the Bacu-lovirus IAP Repeats (BIR) domain within survivin, encompassing both apoptosis and proliferation, through an in silico study. The protein-protein interaction (PPI) network of survivin was analyzed using Cytoscape software. Functional enrichment (FE) analysis and data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to identify the implicated signaling pathways. The binding affinity of the BIR domain with the targeted proteins was visualized via molecular docking analysis. Drawing insights from the PPI network and FE analysis, we identified two key proteins in-volved in apoptosis such as X-linked Inhibitor of Apoptosis Proteins (XIAP) and caspase-9, and proliferation such as Cyclin-dependent Kinase 1 (CDK1) and Inner Centromere Protein (INCENP) for further analysis of their binding with the survivin BIR domain. These proteins were found to bind to the BIR domain at the Thr34, Thr48, and Ser20 resi-dues that have critical roles to regulate the apoptosis and proliferation. This study provides future insights into how the BIR domain of survivin could emerge as a potential target for cancer treatment, such as determining knockout targets for the development of genome editing technology
Tumor apparent diffusion coefficient value and ratio in magnetic resonance imaging on cervical cancer Siregar, Trifonia Pingkan; Wanandi, Septelia Inawati; Darmiati, Sawitri; Kusuma, Fitriyadi; Sekarutami, Sri Mutya; Lisnawati; Prihartono, Joedo; Ilyas, Muhammad; Amalia, Ginva; Elfahmi, Khalida Ikhlasiya Tajdar Gefariena
Medical Journal of Indonesia Vol. 34 No. 2 (2025): June
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.13181/mji.oa.257715

Abstract

BACKGROUND Diffusion-weighted magnetic resonance imaging (DW-MRI) is a noninvasive, non-contrast sequence for cancer detection. Research involving DW-MRI in cervical cancer has revealed lower apparent diffusion coefficient (ADC) values. This study aimed to evaluate the difference in tumor ADC values and ADC ratios (tumor-to-urine and tumor-to-muscle) with respect to tumor staging (early versus late) and histopathology (squamous cell carcinoma versus adenocarcinoma). METHODS This retrospective study included 56 patients with cervical cancer, divided into early- and late-stage groups. DW-MRI was performed in all patients, and the tumor ADC value, ADC ratio between the tumor and urine (ADC ratiot−u), and ADC ratio between the tumor and gluteal muscle (ADC ratiot−m) were measured. Statistical methods were employed to assess the difference in the tumor ADC value, ADC ratiot−u, and ADC ratiot−m with respect to cervical cancer stages and histopathological findings. RESULTS The median tumor ADC value was lower in the early-stage group than in the late-stage cervical cancer (0.75 × 10−3 mm²/s versus 0.8 × 10−3 mm²/s, p = 0.022). However, no differences were observed in ADC ratiot−u and ADC ratiot−m concerning the tumor staging, nor in ADC value, ADC ratiot−u, and ADC ratiot−m concerning histopathological findings (p = 0.29, 0.67 and 0.35, respectively), with no significant differences in the ADC ratiot−u (p = 0.153) and ADC ratiot−m (p = 0.260). In receiver operating characteristic analysis, the tumor ADC value was 75.0% sensitive and 50.0% specific in predicting late-stage cervical cancer with a cut-off value of 0.750 × 10−3 mm2/s. CONCLUSIONS The median tumor ADC value in early-stage patients was significantly lower than in the late-stage patients, suggesting that tumor ADC value has valuable potential for characterizing cervical cancer staging.
Kurkumin Meningkatkan Sensitivitas Sel Kanker Payudara terhadap Tamoksifen Melalui Penghambatan Ekspresi P-glikoprotein dan Breast Cancer Resistance Protein: Curcumin Increased Breast Cancer Cells Sensitivity to Tamoxifen Through Inhibition of P-glycoprotein and Breast Cancer Resistance Protein Expressions Sianipar, Erlia Anggrainy; Louisa, Melva; Wanandi, Septelia Inawati
Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) (e-Journal) Vol. 4 No. 1 (2018): (March 2018)
Publisher : Universitas Tadulako

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (189.335 KB) | DOI: 10.22487/j24428744.2018.v4.i1.9209

Abstract

The decreasing of sensitivity or resistance to tamoxifen occured after long-term treatment in breast cancer. One of the major factor in tamoxifen resistance is over expression of efflux transporter P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). Curcumin has known as inhibitor of P-gp and BCRP. The addition of curcumin to the tamoxifen resistant cells is expected to increase the sensitivity of breast cancer cells to tamoxifen. This study aim to know the effect of curcumin in increasing the cell sensitivity to tamoxifen through inhibition of P-gp and BCRP transporter efflux. MCF-7 breast cancer cell line was induced with tamoxifen 1 µM for 10 passage (MCF-7(T)), then cell viability and mRNA expression of P-gp and BCRP were analyzed. To the MCF-7(T) cells, curcumin was given at of 5/10/20 µM with or without tamoxifen for 5 days and cell viability and mRNA expression of P-gp and BCRP were analyzed on day 5th. As positive control, verapamil 50 µM was used as P-gp inhibitor, ritonavir 15 µM and nelfinavir 15 µM were used as BCRP inhibitor. The results showed that MCF-7(T) cells sensitivity to tamoxifen decreased with 11.8 times, the cell viability increased 10.82 fold and mRNA expression of P-gp and BCRP increased 4.04 fold. Then after administration of curcumin with or without tamoxifen for 5 days, the cell viability and the mRNA expression of P-gp and BCRP decreased. As conclusion, curcumin increased the sensitivity of MCF-7(T) to tamoxifen characterized by the decreasing of cell viability and mRNA expression of P-gp and BCRP. However, the administration of combination of curcumin with tamoxifen was more potent than just curcumin. The increased sensitivity was estimated at least partly through the inhibition of P-gp and BCRP mRNA expression by curcumin
FOXO1 and FYN Expression Trends in Breast Cancer Stem Cells: An Integrative Study of Single Nucleotide Polymorphism (SNP) Array and Quantitative PCR (qPCR) Analysis Margaret, Ay Ly; Wanandi, Septelia Inawati; Fadilah, Fadilah; Paramita, Rafika Indah
The Indonesian Biomedical Journal Vol 17, No 4 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i4.3656

Abstract

BACKGROUND: Currently, identification of breast cancer stem cells (BCSCs) commonly relies on CD24-/CD44+ expression profiles. However, few studies have integrated genomic mutation data with experimental gene expression validation in CSC and non-CSC populations. Genotyping results of CD24-/CD44+ MDAMB-231 cells revealed 36 mutations in BCSCs compared to non-BCSCs, with upregulated FOXO1 and FYN that might represent promising candidate biomarkers for this subpopulation. Therefore, in this study, single nucleotide polymorphism (SNP) and quantitative polymerase chain reaction (qPCR) analysis were performed to assess the association between mutations and expression trends of FOXO1 and FYN in MDAMB-231 cell, as breast cancer cell model with stem-like traits and well-characterized profile.METHODS: Genomic DNA was isolated from BCSC and non-BCSC DNA from the MDAMB-231 cell line. Mutation analysis was conducted using PLINK, while gene expressions of FOXO1 and FYN were quantified by one-step SYBR Green-based qPCR, using 18s rRNA as a reference. Data was then analyzed with the Livak (2−∆∆Ct) method.RESULTS: Among 36 mutations found in BCSCs of the MDAMB-231 cell line, PTEN (rs786204914) and CHEK2 (rs587782401) were identified as pathogenic. While FOXO1 (2.989±2.817 vs. 1.072±0.388) and FYN (1.405±0.072 vs. 0.855±0.140) mRNA levels were found to be higher in CSCs compared to non-CSCs, though these differences was not statistically significant.CONCLUSION: Pathogenic mutations in CHEK2 and PTEN were detected within BCSC population, implying a potential influence on the expression of FOXO1 and FYN, though not statistically significant. These findings suggest a possible, but as yet unverified, association between gene mutations and expression patterns, emphasizing the importance of further functional studies to validate FOXO1 and FYN as biomarkers for BCSCs.KEYWORDS: breast cancer stem cells, FOXO1, FYN, PTEN, CHEK2, mutation, biomarker