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Long non-coding RNAs (lncRNAs) are emerging in molecular biology as crucial regulators of cancer. Although the aberrant expression of lncRNAs has been observed in osteosarcoma (OS), the molecular mechanisms underlying lncRNAs in doxorubicin resistance of OS still unknown. In the current study, we investigated a novel lncRNA, termed ODRUL (osteosarcoma doxorubicin-resistance related up-regulated lncRNA), and evaluated its role in the occurrence of doxorubicin resistance in OS. LncRNA microarray revealed that lncRNA ODRUL was the most up-regulated expressed in the doxorubicin-resistant OS cell line. Quantitative real-time PCR (qRT-PCR) confirmed that lncRNA ODRUL was higher in different doxorubicin-resistant OS cell lines and lower in different doxorubicin-sensitive OS cell lines. Moreover, we showed that lncRNA ODRUL was increased in specimens of OS patients with a poor chemoresponse and lung metastasis. We further demonstrated that lncRNA ODRUL inhibition could inhibit OS cell proliferation, migration, and partly reversed doxorubicin resistance in vitro. In addition, we found that the expression of classical drug resistance-related ATP-binding cassette, subfamily B, member 1 (ABCB1) gene was decreased after the lncRNA ODRUL knockdown. Thus, we concluded that lncRNA ODRUL may act as a pro-doxorubicin-resistant molecule through inducing the expression of the classical multidrug resistance-related ABCB1 gene in osteosarcoma cells .These findings may provide a novel target for reversing doxorubicin resistance in OS.

Background Atherosclerosis is a condition with the vascular accumulation of lipid plaques, and its main major contributing factor is endothelial injury induced by oxidized low-density lipoprotein (ox-LDL). Salidroside (SAL) is the primary active ingredient of Rhodiola rosea , and exhibits antioxidant properties on endothelial cells and alleviates atherosclerosis. However, the effect of SAL on autophagy in ox-LDL-induced vascular endothelial injury remains unclear. Here, we investigated the effect and underlying mechanisms of SAL on autophagy in human umbilical vein endothelial cells (HUVECs). Methods HUVECs were incubated with ox-LDL to induce in vitro atherosclerosis model. The cell viability and injury were evaluated by cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release assay. The oxidative stress was evaluated by NADPH oxidase, malondialdehyde (MDA) and superoxide dismutase (SOD) activities. Immunofluorescence was performed to detect autophagy using LC3β antibody. Quantitative real-time PCR (qRT-PCR) and western blot were performed to measure the mRNA expressions of SIRT1 and Forkhead box O1 (FOXO1). Nicotinamide (NAM) and AS1842856 were used to inhibit activities of SIRT1 and FOXO1, respectively. Results Exposure of HUVECs to ox-LDL (100 μg/mL) reduced cell viability, increased cellular MDA, and reduced SOD in a concentration-dependent manner. The pretreatment with SAL (20, 50 and 100 μM) significantly enhanced the cell viability and decreased LDH release in HUVECs exposed to ox-LDL (100 μg/mL). ox-LDL induced autophagy in HUVECs, which was further enhanced by pretreatment with SAL. However, SAL attenuated increase in oxidative stress in HUVECs induced by ox-LDL. ox-LDL reduced mRNA and protein expressions of SIRT1 and FOXO1, which could be reversed by SAL. The protective, anti-oxidative and pro-autophagic effects of SAL could be obviously abolished by cotreatment with SIRT1 inhibitor or FOXO1 inhibitor. Conclusion Salidroside shows protective effect on endothelial cell induced by ox-LDL, and the mechanisms might be related to autophagy induction via increasing SIRT1 and FoxO1 expressions.