LncRNA‐HOTAIRM1 promotes aerobic glycolysis and proliferation in osteosarcoma via the miR‐664b‐3p/Rheb/mTOR pathway

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.