DNA demethylating agent 5-aza-2'-deoxycytidine and histone deacetylase inhibitor 4-phenylbutyric acid, or transfection with miR-10b mimics promoted the expression of miR-10b,

MicroRNAs (miRs) can lead to mRNA degradation or inhibit protein translation through directly binding to the 3'-untranslational region (UTR) of their target mRNAs. Deregulation of miR-10b has been reported to be associated with chondrosarcoma. However, the role of miR-10b in chondrosarcoma cell migration and invasion, as well as the underlying mechanisms, has not been investigated. In the present study, it was demonstrated that miR-10b was notably downregulated in the JJ012 and SW1353 chondrosarcoma cell lines compared with the TC28a2 normal chondrocyte line. Treatment with DNA demethylating agent 5-aza-2'-deoxycytidine and histone deacetylase inhibitor 4-phenylbutyric acid, or transfection with miR-10b mimics promoted the expression of miR-10b, which further suppressed the migratory and invasive capacities of JJ012 chondrosarcoma cells. Moreover, brain-derived neurotrophic factor (BDNF) was identified as a novel target of miR-10b, and its protein expression level was negatively regulated by miR-10b in JJ012 cells. Furthermore, overexpression of BDNF reversed the inhibitory effect of miR-10b upregulation on the migration and invasion of JJ012 cells. In addition, the data suggest that matrix metalloproteinase 1 (MMP1) may be involved in the miR-10b/BDNF-mediated chondrosarcoma cell migration and invasion in JJ012 cells. In conclusion, these findings suggest that miR‐10b/BDNF may serve as a potential therapeutic target for chondrosarcoma. Introduction Chondrosarcoma, a mesenchymal tumor with unknown cause and differentiation status, is one of the most common types of primary bone cancer developing in cartilage cells. Despite improvements in adjuvant treatments, including surgical resection, radiotherapy and chemotherapy, the prognosis of patients with chondrosarcoma remains poor (1,2). Thus investigation into potential therapeutic targets for chondrosarcoma remains a priority to decrease mortality rates. MicroRNA (miRs), a type of non-coding RNA, can lead to mRNA degradation or inhibit protein translation through directly binding to the 3'-untranslational region (UTR) of their target mRNAs (3). Through mediating the expression of their target genes, miRs participate in various biological processes, such as cell proliferation, differentiation, survival, apoptosis, cell cycle progression and migration (4). Furthermore, deregulation of miRs has been found to be key in various types of human cancer, including chondrosarcoma (5,6). For instance, miR-518b was involved in Gallic acid-induced apoptosis and migration inhibition in chondrosarcoma cells (7). Deregulation of miR-10b has been demonstrated to be associated with multiple types of cancer, such as non-small cell lung, breast, bladder and gastric cancer (8-11). Recently, Yoshitaka et al (12) performed analysis of miRs in chondrosarcoma, and found that the expression of miR-10b was markedly reduced in chondrosarcoma cells compared with non-tumorous articular chondrocytes, suggesting that deregulation of miR-10b may be involved in the tumorigenesis of chondrosarcoma. However, the exact role of miR-10b in mediating the migratory and invasive capacities of chondrosarcoma cells, as well as the underlying mechanisms, remains largely unknown. The present study aimed to reveal the role of miR-10b in mediating the migratory and invasive capacities of chondrosarcoma cells. In addition, the underlying molecular mechanisms were also investigated. Materials and methods Reagen ts a nd m ater ia ls. Demethyla t ion agent, 5-5-Aza-2'-deoxycytidine (5-Aza), and histone deacetylase MicroRNA‐10b suppresses the migration and invasion of chondrosarcoma cells by targeting brain‐derived neurotrophic factor ABUDUNAIBI AILI1,2, YONG CHEN1 and HONGQI ZHANG1 1Department of Spinal Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008; 2Department of Spinal Surgery, The Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830002, P.R. China Received November 12, 2014; Accepted August 17, 2015 DOI: 10.3892/mmr.2015.4506 Correspondence to: Professor Hongqi Zhang, Department of Spinal Surgery, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, Hunan 410008, P.R. China E-mail: [email protected]