MicroRNA‑545‑5p regulates apoptosis, migration and invasion of osteosarcoma by targeting dimethyladenosine transferase 1

Abstract

The metastasis of osteosarcoma is a major threat to both adolescents and young adults. Identifying novel targets that may prevent osteosarcoma metastasis is critical in developing advanced clinical therapies for treating this cancer. The present study aimed to explore the mechanism of microRNA (miR)-545-5p in the metastasis of osteosarcoma. The present study identified miR-545-5p as a potential target that was downregulated in both osteosarcoma clinical samples and cell lines, and in the latter, ectopically expressed miR-545-5p caused apoptosis. In addition, miR-545-5p exerted inhibitory effects in osteosarcoma migration and invasion. Overexpression of miR-545-5p induced xenograft growth inhibition in vivo. In addition, miR-545-5p targeted dimethyladenosine transferase 1 (DIMT1), an oncogenic protein that facilitates osteosarcoma proliferation, migration and invasion. Taken together, the results of the present study suggest that miR-545-5p functions as a tumor suppressor in osteosarcoma that promotes apoptosis, while inhibiting migration and invasion by targeting DIMT1. Taken together, the results of the present study suggest two potential novel targets for osteosarcoma treatment and metastasis prevention.

Current and future perspectives on the regulation and functions of miR-545 in cancer development

“…For example, it promotes tumor growth via four targets in LC ( CCND1 14 and CDK4 14 ) and OC ( PLK1 52 and KDM4B 52 ) but inhibits tumor growth in HCC via two targets ( RIG-I 8 and MT1M 53 ). Additionally, miR-545-5p promotes tumor growth in animal models of NSCLC and SaOS by targeting c-Met 45 and DIMT1, 9 respectively.…”

“… 53 Additionally, miR-545-5p promotes cancer cell invasion and migration by targeting six genes: CCND2 in NPC, 44 SSFA2 in LC, 36 c-MET in NSCLC, 45 CNPY2 in GC, 61 MDM2 in CRC, 48 and DIMT1 in SaOS. 9 …”

“…miR-545 is located at Xq13.2, within intron 1 of the lncRNA FTX ( FTX Transcript, XIST Regulator), and it has been associated with cancers in multiple systems, including the nervous, 4 , 5 respiratory, 6 , 7 digestive 8 and motor 9 systems. miR-545 is intricately involved in an extensive ceRNA regulatory network, and it is competitively repressed by 15 circRNAs and 12 lncRNAs.…”