Long noncoding RNA CASC11 promotes osteosarcoma metastasis by suppressing degradation of snail mRNA

长链非编码 RNA CASC11 通过抑制蜗牛 mRNA 降解促进骨肉瘤转移

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作者:Kaifang Song, Xiang Yuan, Guifang Li, Mingyang Ma, Jiangtao Sun

Abstract

Osteosarcoma (OS) is the most common primary bone tumor in adolescents. Dysregulation of long noncoding RNAs (lncRNAs) is associated with the cancer progression, of which cancer susceptibility candidate 11 (CASC11) has been indicated as an oncogene in several human cancers. However, the underlying mechanisms by which CASC11 contributes to OS metastasis remain undetermined. Here, we found that CASC11 expression in OS tissues was markedly higher than that in noncancerous tissues. Clinical association analysis revealed that high CASC11 expression correlated with clinical stage, distant metastasis and poor prognosis of OS patients. Gain- and loss-of-function assays demonstrated that CASC11 promoted migration, invasion, epithelial-mesenchymal transition (EMT) and metastasis of OS cells in vitro and in vivo. CASC11 associated with the EMT inducer Snail mRNA and increased its stability. Association of CASC11 with Snail mRNA blocked the repressing effect of miR-122, miR-145, miR-211, miR-34a and miR-137 on Snail. Moreover, CASC11-specific siRNAs significantly inhibit tumor metastasis in vivo. Taken together, our findings suggest that CASC11 may be a candidate prognostic biomarker and a novel therapeutic target for OS.

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