| Affiliation: | 1. Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China;2. Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China Dalian Medical University, Dalian, China;3. Changzhou No.6 People's Hospital, Nanjing Medical University, Changzhou, China |
| 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. |
