ArticleGynecologic oncology2016
Transmembrane protein 88 (TMEM88) promoter hypomethylation is associated with platinum resistance in ovarian cancer.
Article in Gynecologic oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Meta-analysis of microarray data to determine gene indicators involved in the cisplatin resistance in ovarian cancer.Cancer reports (Hoboken, N.J.) · 2023Pooled it
- TMEM44 as a Novel Prognostic Marker for Hepatocellular Carcinoma is Associated with Tumor Invasion, Migration, and Apoptosis.Biochemical genetics · 2026Article
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Targeting epigenetic networks to overcome cisplatin resistance in ovarian cancer: from mechanisms to clinical translation.Journal of ovarian research · 2026Review
- TMEM88 modulates the proliferation and metastasis of HCC via the GSK-3β/β-catenin pathway.BMC cancer · 2025Article
- Epigenetics in Ovarian Cancer: A Review of Current Knowledge and Future Perspectives.Biomedicines · 2025Review
- MBNL2 enhances cisplatin resistance by regulating apoptosis in ovarian cancer cells.BMB reports · 2025Article
- The roles and functions of TMEM protein family members in cancers, cardiovascular and kidney diseases (Review).Biomedical reports · 2025Review
- The emerging role of transmembrane proteins in tumorigenesis and therapy.Translational cancer research · 2025Review
- TMEM205 induces TAM/M2 polarization to promote cisplatin resistance in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- The Clinical Significance ofInternational journal of molecular sciences · 2024Article
- Current data and future perspectives on DNA methylation in ovarian cancer (Review).International journal of oncology · 2024Review
- TMEM44 as a Novel Prognostic Marker for Kidney Renal Clear Cell Carcinoma is Associated with Tumor Invasion, Migration and Immune Infiltration.Biochemical genetics · 2024Article
- Association between single nucleotide polymorphisms, TGF-β1 promoter methylation, and polycystic ovary syndrome.BMC pregnancy and childbirth · 2024Article
- Identification of immune cell infiltration and effective biomarkers of polycystic ovary syndrome by bioinformatics analysis.BMC pregnancy and childbirth · 2023Article
- The role of DNA methylation in ovarian cancer chemoresistance: A narrative review.Health science reports · 2023Article
- TMEM196 inhibits lung cancer metastasis by regulating the Wnt/β-catenin signaling pathway.Journal of cancer research and clinical oncology · 2023Article
- Transmembrane protein 88 suppresses hepatocellular carcinoma progression and serves as a novel prognostic factor.Frontiers in oncology · 2023Article
- DNA Methylation Biomarkers for Prediction of Response to Platinum-Based Chemotherapy: Where Do We Stand?Cancers · 2022Review
- Revisiting chemoresistance in ovarian cancer: Mechanism, biomarkers, and precision medicine.Genes & diseases · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesEpigenetic alterations have been implicated in the development of platinum resistance in ovarian cancer (OC). In this study, we aimed to identify DNA methylation changes in platinum resistant tumors and their functional implications.
methodsTo identify DNA methylation alterations we used the Illumina 450k DNA methylation array and profiled platinum sensitive and resistant OC xenografts. Validation analyses employed RT-PCR and immunohistochemistry (IHC).
resultsGenome-wide DNA methylation analysis of OC xenografts identified 6 genes (SSH3, SLC12A4, TMEM88, PCDHGC3, DAXX, MEST) whose promoters were significantly hypomethylated in resistant compared to sensitive (control) xenografts (p<0.001). We confirmed that TMEM88 and DAXX mRNA expression levels were increased in platinum resistant compared to control xenografts, inversely correlated with promoter methylation levels. Furthermore treatment of OC cells with SGI-110 (guadecitabine), a DNA methyl transferase (DNMT) inhibitor, increased TMEM88 mRNA expression levels, supporting that TMEM88 is transcriptionally regulated by promoter methylation. TMEM88 was detectable by IHC in all histological types of ovarian tumors and its knock-down by using siRNA promoted OC cell proliferation and colony formation and re-sensitized cells to platinum. Furthermore, TMEM88 knock down induced upregulation of cyclin D1 and c-Myc, known Wnt target genes, supporting that TMEM88 inhibits Wnt signaling.
conclusionsOverall, our results support that OC platinum resistance was correlated with TMEM88 overexpression regulated through decreased promoter methylation. Our data suggest that TMEM88 functions as an inhibitor of Wnt signaling, contributing to the development of platinum resistance.
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