ArticleTranslational cancer research2020
Denosumab inhibits MCF-7 cell line-induced spontaneous osteoclastogenesis via the RANKL/MALAT1/miR-124 axis.
Article in Translational cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- Review
- A potential function for MicroRNA-124 in normal and pathological bone conditions.Non-coding RNA research · 2024Review
- To investigate the role and potential mechanism of has_circ_RBMS3 in bone metastasis of breast cancer based on bioinformatics.Cell biochemistry and biophysics · 2024Article
- What enlightenment has the development of lung cancer bone metastasis brought in the last 22 years.World journal of clinical oncology · 2024Article
- A Machine Learning-Based Image Segmentation Method to Quantify In Vitro Osteoclast Culture Endpoints.Calcified tissue international · 2023Article
- Review
- The regulatory activities of MALAT1 in the development of bone and cartilage diseases.Frontiers in endocrinology · 2022Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDenosumab is an inhibitor of receptor activator of NF-κB ligand (RANKL), which inhibits bone metastasis (BM) in breast cancer (BC), but does not completely control cancer cell BM in some BC patients. This study was designed to study whether denosumab inhibits human BC cells (MCF-7) cell line-induced spontaneous osteoclastogenesis via RANKL/metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-124 axis.
methodsWe established a co-culture system of MCF-7-induced spontaneous osteoclastogenesis in RAW 264.7 cells, and denosumab is added into the co-culture system to inhibit RAW 264.7 cell differentiation into osteoclasts. Real-time PCR (RT-PCR), immunofluorescence and western blotting analysis were used to detect gene expression, while tartrate-resistant acid phosphatase (TRAP) staining was used to assess osteoclast formation.
resultsDenosumab inhibits MCF-7 cell line-induced spontaneous osteoclastogenesis, and the inhibition of denosumab was found to be more pronounced after MALAT1 downregulation and miR-124 overexpression. However, MALAT1 knockdown or miR-124 overexpression did not alter RANKL protein expression. Moreover, the dual luciferase gene reporter system showed that miR-124 targeted the inhibition of MALAT1, while si-MALAT1 upregulated miR-124 expression. miR-124-mimics were able to decrease the expression of Rab27a, IL-11, activated T-cell nuclear factor 1 (NFATc1) and TARP protein.
conclusionsDenosumab inhibits MALAT1 expression by inhibiting RANKL, thereby upregulating miR-124 expression, which ultimately inhibits MCF-7 cell line-induced pseudo osteoclastogenesis.
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