MicroRNA PC-3p-2869 Regulates Antler Growth and Inhibits Proliferation and Migration of Human Osteosarcoma and Chondrosarcoma Cells by Targeting CDK8, EEF1A1, and NTN1.

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.

Antler-derived microRNA PC-5p-1090 inhibits HCC cell proliferation, migration, and invasion by targeting MARCKS, SMARCAD1, and SOX9.

The capability of microRNAs (miRNAs) to regulate gene expression across species has opened new avenues for miRNA-based therapeutics. Here, we investigated the potential of PC-5p-1090 (miR-PC-1090), a miRNA found in deer antlers, to control the malignant phenotypes of hepatocellular carcinoma (HCC) cells. Using Cell Counting Kit-8 and transwell assays, we found that heterologous expression of miR-PC-1090 inhibited HCC cell proliferation, migration, and invasion. Bioinformatics analysis indicated that predicted miR-PC-1090 targets, including MARCKS, SMARCAD1, and SOX9, were significantly elevated in HCC tissues, and their high expressions were associated with poor overall survival of HCC patients. Moreover, mechanistic investigations revealed that miR-PC-1090 promoted the degradation of MARCKS and SMARCAD1 mRNAs and hindered the translation of SOX9 mRNA by recognizing their 3' untranslated regions. Subsequent loss-of-function and rescue experiments confirmed the involvement of MARCKS, SMARCAD1, and SOX9 in miR-PC-1090-suppressed HCC cell proliferation, migration, and invasion. Notably, MARCKS knockdown induced the downregulation of phosphorylated MARCKS and a corresponding upregulation of phosphorylated AKT in HCC. Conversely, miR-PC-1090 repressed MARCKS phosphorylation and effectively circumvented the activation of the PI3K/AKT pathway. Furthermore, miR-PC-1090 regulates the Wnt/ß-catenin pathway through SMARCAD1- and SOX9-mediated reduction of ß-catenin expression. Overall, our results illustrate the tumor-suppressive activity and molecular mechanism of antler-derived miR-PC-1090 in HCC cells, indicating its potential as a multiple-target agent for HCC treatment.