Metabolic switch from oxidative phosphorylation to aerobic glycolysis, which is also called the Warburg effect, is a hallmark of osteosarcoma (OS) and leads to the enhancement of cell chemoresistance, growth, metastasis, and invasion. Emerging evidence indicates that long non-coding RNA (lncRNA) plays a crucial role in the Warburg effect of cancer cells. Here, we report that lncRNA KCNQ1OT1 was upregulated in OS. Meanwhile, functional experiments demonstrated that the KCNQ1OT1 facilitated proliferation and suppressed apoptosis of OS cells. In addition, KCNQ1OT1 contributed to the Warburg effect by stimulating aldolase A (ALDOA) expression. Furthermore, using bioinformatics analysis, luciferase reporter, RNA immunoprecipitation, and RNA pull-down assay, we identified that KCNQ1OT1 functions as a competing endogenous RNA (ceRNA) by sponging miR-34c-5p, which inhibited ALDOA expression by directly targeting its 3ʹUTR. Taken together, these data identified a key role of KCNQ1OT1 in glucose metabolism reprogramming of OS. Targeting the KCNQ1OT1/miR-34c-5p/ALDOA axis may be a potential therapeutic target in OS treatment.

Object. The authors performed a retrospective study of clinical and radiological data obtained in 27 Chinese patients with myelopathy induced by ossification of the ligamentum flavum (OLF) who underwent surgery between March 1990 and March 2002. The factors related to surgical outcome of thoracic OLF-induced myelopathy were also assessed. Methods. The preoperative clinical features and radiological findings were reviewed retrospectively. Preoperative and postoperative neurological status was assessed using the Japanese Orthopaedic Association (JOA) scoring system and the Nurick Scale. The ossified lesions were classified into five types (lateral, extended, enlarged, fused, and tuberous). Multiple linear regression and logistic regression analyses were performed to establish the factors affecting surgical outcome. The patients' chief complaints were lower-limb weakness and gait disturbance (93%), numbness and sensory deficit (89%), and low-back pain (48%). The coexisting pathological entities were disc herniation, canal stenosis, and ossification of posterior longitudinal ligament. The ossified ligamentum flavum was mainly located at the T10–12 (67%) and T1–3 (15%) levels. Symptoms in 26 patients improved but resolved completely in only 14 after surgery. The mean overall JOA score was 5.3 ± 1.9 preoperatively and 7.9 ± 2.3 postoperatively. There is a significant difference between the pre- and postoperative neurological status (p < 0.05) determined by the Student t-test. The recovery rate was 46.3 ± 9.4%. Multiple regression analysis revealed negative correlation between the duration of preoperative symptoms and surgical outcome as well as a positive correlation between the preoperative JOA score and surgical outcome. Logistic regression analysis demonstrated that fecal and/or urinary incontinence, positive patellar and/or ankle clonus, and intramedullary high T2-weighted magnetic resonance (MR) imaging signal change had negative effects on the surgical outcome. Conclusions. The clinical and radiological features of OLF in the Chinese population are similar to those observed in the Japanese population. The duration of preoperative symptoms and JOA score are the most important predictors of the postoperative JOA score and recovery rate. The patients with fecal and/or urinary incontinence, positive patellar and/or ankle clonus, and intramedullary high T2-weighted MR imaging signal change were at higher risk of poor outcome after surgery.

5.