AI Article Synopsis

  • * Overexpressing miR-509-3p in various OS cell lines, including metastatic ones, reduces cell migration, proliferation, and invasion, while also enhancing sensitivity to cisplatin chemotherapy.
  • * The study suggests that miR-509-3p influences key proteins like ARHGAP1 and AXL, which could lead to new therapeutic targets for treating drug-resistant metastatic osteosarcoma.

Article Abstract

Osteosarcoma (OS) is the most common primary pediatric malignancy of the bone having poor prognosis and long-term survival rates of less than 30% in patients with metastasis. MicroRNA-509 was reported to be downregulated in OS. We and others previously published that miR-509-3p can strongly attenuate cellular migration/invasion and sensitize ovarian cancer to cisplatin. Here, we show that overexpression of miR-509-3p inhibited migration of primary OS cell lines U2OS, HOS, and SaOS2 as well as metastatic derivatives 143B and LM7. miR-509-3p overexpression also inhibited proliferation and invasion of HOS and 143B cells and sensitized cells to cisplatin. Luciferase reporter assays using 3'-UTRs of predicted miR-509-3p targets associated with metastatic phenotypes revealed ARHGAP1 could be one of the downstream effectors of miR-509-3p in HOS. To find the global impact of miR-509-3p overexpression and cisplatin treatment we performed Reverse Phase Protein Analysis (RPPA). AXL, which has been reported to play a critical role in cisplatin resistance and confirmed as direct target of miR-509-3p was downregulated upon miR-509-3p treatment and further down-regulated upon miR-509-3p + cisplatin treatment. We propose that the miR-509-3p/AXL and miR-509-3p/ARHGAP1 axes have the potential to uncover new druggable targets for the treatment of drug resistant metastatic osteosarcoma.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911094PMC
http://dx.doi.org/10.1038/s41598-019-55170-2DOI Listing

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