Abstract
Osteosarcoma (OS) is one of the most common primary bone malignancies and accounts for 3.4% of pediatric tumors. Its 5-year survival is as low as about 20%. Differentially expressed lncRNAs in OS profiling were searched in the downloaded profile of GSE12865. As a result, LINC00266-1 was detected to be upregulated in both GSE12865 and OS tissues we collected. SMAD2 was the downstream target binding to promoter sites of LINC00266-1, displaying a positive regulatory interaction. Knockdown of LINC00266-1 suppressed the proliferative and metastatic abilities, and promoted the apoptosis in OS cells. Besides, knockdown of LINC00266-1 significantly alleviated the growth of OS in vivo. MiR-548c-3p was the sponge miRNA of LINC00266-1, which was able to reverse the regulatory effects of LINC00266-1 on OS cell phenotypes. Moreover, miR-548c-3p bound to the 3′-UTR of SMAD2 and thus downregulated SMAD2. Overexpression of SMAD2 partially reversed the regulatory effects of LINC00266-1 on OS cell phenotypes. Finally, we have identified that LINC00266-1/miR-548c-3p/SMAD2 feedback loop was responsible for stimulating the development of OS.
Highlights
Osteosarcoma (OS) is a prevalent primary bone malignancy that mainly affects adolescents
We mainly focused on upregulated lncRNAs because they may be more readily used as early diagnostic markers or therapeutic targets
We first demonstrated that LINC00266-1 was highly expressed in OS tissues
Summary
Osteosarcoma (OS) is a prevalent primary bone malignancy that mainly affects adolescents. Osteosarcoma accounts for 3.4% of pediatric tumor cases[1]. Surgery combined with chemotherapy has been widely applied for the treatment of OS, the 5-year survival rate of OS is only 20% because of its potent invasiveness, high metastatic rate and recurrence[2]. It is necessary to explore the key mechanisms underlying the development of OS, improving the therapeutic efficacy of its treatments and its prognosis. With the development of whole-genome sequencing technology, it was determined that protein-coding sequences account for less than 2% of the human genome[3]. LncRNAs (long noncoding RNAs) are noncoding RNAs
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