PDF(Pubmed)
Abstract：
Osteosarcoma (OS), which is a common and aggressive primary bone malignancy, occurs mainly in children and adolescent. Long noncoding RNAs (lncRNAs) are reported to play a pivotal role in various cancers. Here, we found that the lncRNA HOTAIRM1 is upregulated in OS cells and tissues. A set of functional experiments suggested that HOTAIRM1 knockdown attenuated the proliferation and stimulated the apoptosis of OS cells. A subsequent mechanistic study revealed that HOTAIRM1 functions as a competing endogenous RNA to elevate ras homologue enriched in brain (Rheb) expression by sponging miR-664b-3p. Immediately afterward, upregulated Rheb facilitates proliferation and suppresses apoptosis by promoting the mTOR pathway-mediated Warburg effect in OS. In summary, our findings demonstrated that HOTAIRM1 promotes the proliferation and suppresses the apoptosis of OS cells by enhancing the Warburg effect via the miR-664b-3p/Rheb/mTOR axis. Understanding the underlying mechanisms and targeting the HOTAIRM1/miR-664b-3p/Rheb/mTOR axis are essential for OS clinical treatment.
摘要：
骨肉瘤(OS),这是一种常见的侵袭性原发性骨恶性肿瘤，主要发生在儿童和青少年。据报道，长链非编码RNA（lncRNA）在各种癌症中起关键作用。这里,我们发现lncRNAHOTAIRM1在OS细胞和组织中上调。一系列功能实验表明，HOTAIRM1敲低可减弱OS细胞的增殖并刺激其凋亡。随后的机理研究表明，HOTAIRM1作为竞争性内源性RNA发挥功能，通过形成miR-664b-3p来提高富含脑（Rheb）表达的ras同源物。紧接着，上调的Rheb通过促进OS中mTOR通路介导的Warburg效应促进增殖并抑制细胞凋亡。总之,我们的研究结果表明,HOTAIRM1通过miR-664b-3p/Rheb/mTOR轴增强Warburg效应,从而促进OS细胞的增殖并抑制其凋亡.了解潜在机制和靶向HOTAIRM1/miR-664b-3p/Rheb/mTOR轴对于OS临床治疗至关重要。
