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Abstract
Recently, several long non-coding RNAs (lncRNAs) have been implicated in osteosarcoma (OS). However, the regulatory roles of lncRNAs in chemotherapy resistance of OS still remain unclear. This study aimed to screen a novel lncRNA that contributes to chemotherapeutic resistance of OS, and to explore the underlying mechanisms. Our data showed that lncRNA CTA was markedly downregulated in OS tissues compared to their matched non-tumor tissues, and low expression of lncRNA CTA was significantly associated with the advanced clinical stage and tumor size. In addition, OS patients with low lncRNA CTA levels showed a worse prognosis when compared with those with high expression of lncRNA CTA. Furthermore, we report that lncRNA CTA has an inverse relationship with miR-210 expression in OS tissues. LncRNA CTA could be activated by doxorubicin (DOX), and could promote OS cell apoptosis by competitively binding miR-210, while inhibit cell autophagy. On the other hand, lncRNA CTA was downregulated in DOX-resistant OS cells. Overexpression of lncRNA CTA reduced autophagy and subsequently overcame DOX resistance of OS in vitro and in vivo. Therefore, we demonstrate that lncRNA CTA is an essential regulator in DOX-induced OS cell apoptosis, and the lncRNA CTA-miR-210 axis plays an important role in reducing OS chemoresistance.
Highlights
Osteosarcoma (OS) is the most common cancer in bone with poor prognosis, mainly due to chemotherapy resistance [1]
Increasing studies have shown that long non-coding RNA (lncRNA) play an important role in tumorigenesis and chemoresistance [24, 25], but little is known about the DOX-induced lncRNAs in osteosarcoma cells
We observed that lncRNA CTA was markedly decreased in osteosarcoma tissues, and low expression of lncRNA CTA predicted a poor prognosis of patients with osteosarcoma
Summary
Osteosarcoma (OS) is the most common cancer in bone with poor prognosis, mainly due to chemotherapy resistance [1]. Emerging evidence have revealed that non-coding RNAs including long non-coding RNA (lncRNA) and microRNAs (miRs) are involved in drug resistance [2, 3]. Various miRs have been found to may become potential therapeutic targets or candidates for osteosarcoma [7]. Dysregulation of miR-210 directly modulates changes in mRNA transcription associated with aberrant regulation of cell morphology and metastasis [10]. Increased levels of miR-210 expression are associated with poor cancer patient outcomes, including pancreatic ductal adenocarcinoma [13], glioma [14], and breast cancer [15]. MiR-210 acts as an oncogene in many types of cancers, and has been the most extensively studied
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