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MicroRNA PC-3p-2869 Regulates Antler Growth and Inhibits Proliferation and Migration of Human Osteosarcoma and
Fan Yang1, Jin Wu1, Mindie Zhao1
1Laboratory of Genetics and Molecular Biology, College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China.
Abstract:
MicroRNAs (miRNAs) play a crucial role in maintaining the balance between the rapid growth and suppression of tumorigenesis during antler regeneration. This study investigated the role of a novel miRNA, PC-3p-2869 (miR-PC-2869), in antler growth and its therapeutic potential in human osteosarcoma and chondrosarcoma. Stem-loop RT-qPCR showed that miR-PC-2869 was expressed extensively in diverse layers of antler tissues. Overexpression of miR-PC-2869 suppressed the proliferation and migration of antler cartilage cells. Similarly, heterologous expression of miR-PC-2869 reduced the proliferation, colony formation, and migration of osteosarcoma cell line MG63 and U2OS and chondrosarcoma cell line SW1353. Moreover, 18 functional target genes of miR-PC-2869 in humans were identified based on the screening of the reporter library. Among them, 15 target genes, including CDK8, EEF1A1, and NTN1, possess conserved miR-PC-2869-binding sites between humans and red deer (Cervus elaphus). In line with this, miR-PC-2869 overexpression decreased the expression levels of CDK8, EEF1A1, and NTN1 in MG63, SW1353, and antler cartilage cells. As expected, the knockdown of CDK8, EEF1A1, or NTN1 inhibited the proliferation and migration of MG63, SW1353, and antler cartilage cells, demonstrating similar suppressive effects as miR-PC-2869 overexpression. Furthermore, we observed that CDK8, EEF1A1, and NTN1 mediated the regulation of c-myc and cyclin D1 by miR-PC-2869 in MG63, SW1353, and antler cartilage cells. Overall, our work uncovered the cellular functions and underlying molecular mechanism of antler-derived miR-PC-2869, highlighting its potential as a therapeutic candidate for bone cancer.
Insights
A novel microRNA (miRNA) from deer antlers, miR-PC-2869, suppresses bone cancer cell growth. This discovery highlights its potential as a new therapeutic for osteosarcoma and chondrosarcoma.
Area of Science:
- Molecular Biology
- Cancer Research
- Regenerative Medicine
Background:
- MicroRNAs (miRNAs) are critical regulators of cellular processes, including tumorigenesis and tissue regeneration.
- Antler regeneration involves a complex interplay between cell growth and suppression, with miRNAs playing a key role.
- The therapeutic potential of naturally occurring molecules in regenerative processes for cancer treatment is an area of active investigation.
Purpose of the Study:
- To investigate the role of a novel antler-derived microRNA, PC-3p-2869 (miR-PC-2869), in antler growth regulation.
- To explore the therapeutic potential of miR-PC-2869 in human osteosarcoma and chondrosarcoma cell lines.
- To elucidate the molecular mechanism underlying miR-PC-2869's function and its target genes.
Main Methods:
- Stem-loop RT-qPCR was used to detect miR-PC-2869 expression in antler tissues.
- Overexpression and knockdown experiments were performed in antler cartilage cells and human bone cancer cell lines (MG63, U2OS, SW1353).
- Reporter assays were employed to identify functional target genes of miR-PC-2869, followed by expression analysis and mechanistic studies involving c-myc and cyclin D1.
Main Results:
- miR-PC-2869 was widely expressed in antler tissues and suppressed the proliferation and migration of antler cartilage cells.
- Heterologous expression of miR-PC-2869 significantly reduced proliferation, colony formation, and migration in osteosarcoma and chondrosarcoma cell lines.
- miR-PC-2869 targets conserved genes (e.g., CDK8, EEF1A1, NTN1) that mediate the regulation of c-myc and cyclin D1, explaining its anti-cancer effects.
Conclusions:
- Antler-derived miR-PC-2869 functions as a tumor suppressor by inhibiting cell proliferation and migration.
- The identified target genes CDK8, EEF1A1, and NTN1 are crucial mediators of miR-PC-2869's anti-cancer activity.
- miR-PC-2869 represents a promising therapeutic candidate for human osteosarcoma and chondrosarcoma.
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