ArticleCancer cell international2022
DNA methyltransferase 1 inhibits microRNA-497 and elevates GPRC5A expression to promote chemotherapy resistance and metastasis in breast cancer.
Article in Cancer cell international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Multi-omics characterization of a GPRC5AJournal of translational medicine · 2026Article
- Article
- Study on Abnormal Angiogenesis in Moyamoya Disease via Mitochondrial D-Loop Methylation.Brain and behavior · 2025Article
- Autophagy mediated immune response regulation and drug resistance in cancer.Molecular biology reports · 2025Review
- A Comprehensive Review on LncRNAs/miRNAs-DNMT1 Axis in Human Cancer: Mechanistic and Clinical Application.Journal of cellular and molecular medicine · 2025Review
- Nanotechnology in cancer treatment: revolutionizing strategies against drug resistance.Frontiers in bioengineering and biotechnology · 2025Review
- Review
- Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics.International journal of molecular sciences · 2022Review
- Longitude Variation of the microRNA-497/FGF-23 Axis during Treatment and Its Linkage with Neoadjuvant/Adjuvant Trastuzumab-Induced Cardiotoxicity in HER2-Positive Breast Cancer Patients.Frontiers in surgery · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAbnormal DNA methylation of tumor suppressor gene promoter has been found in breast cancer. Therefore, the current study set out to explore how DNA methyltransferase 1 (DNMT1) affects breast cancer through mediating miR-497/GPRC5A axis.
methodsAfter loss and gain-of-function approaches were conducted in MCF-7/ADR and MCF-7 cells, cell viability, IC50 value, invasion, migration and apoptosis were measured, respectively. In addition, drug resistance, metastasis and apoptosis-related protein expression were examined using immunoblotting. ChIP and dual-luciferase reporter gene assays were carried out to validate relationship among DNMT1, miR-497, and GPRC5RA. Subcutaneous xenograft tumor model in nude mice was established to detect effects of DNMT1 on growth and metastasis of breast cancer in vivo.
resultsIt was found that DNMT1 was notably increased, while miR-497 was poorly-expressed in breast cancer. Highly-expressed DNMT1 could promote chemotherapy resistance and metastasis of breast cancer. Meanwhile, DNMT1 modified methylation of CpG island in miR-497 promoter region, thereby repressing miR-497 level. In addition, miR-497 targeted GPRC5A expression to curb chemotherapy resistance and metastasis of breast cancer cells. Lastly, in vivo experiments showed that knockdown of DNMT1 could suppress breast cancer growth and metastasis.
conclusionsCollectively, our findings indicated that DNMT1 may inhibit miR-497 and boost the expression of GPRC5A through methylation, thus augmenting breast cancer chemotherapy resistance and metastasis, which provides novel mechanistic insight into the unrecognized roles of DNMT1 in breast cancer.
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