RESUMEN
BACKGROUND: Chemokines have been identified to be involved in the modulation of pain through both peripheral and central mechanisms. However, the role of chemokines in lumbar disk herniation (LDH) with sciatic pain remains unknown. OBJECTIVE: The current study was performed to explore the expression of two most commonly studied chemokines CX3CL1 and CCL2 and assess their associations with clinical severity in LDH patients with sciatic pain. METHODS: The soft tissues around nerve root (STANR), annulus fibrosus (AF), and nucleus pulposus (NP) biopsies were obtained from 36 LDH patients with chronic sciatic pain and 10 scoliosis patients (painless controls). The serum and local expressions of CX3CL1 and CCL2 were determined using enzyme-linked immunosorbent assay and Western blot analysis, respectively. The visual analog scale (VAS) scores for low back pain and lower extremity pain and Japanese Orthopaedic Association (JOA) scores were recorded on the day of hospital admission to evaluate the clinical severity. LDH patients with sciatic pain were divided into severe pain (SP) group (VAS ≥7; n=18) and mild-to-moderate pain (M-MP) group (VAS <7; n=18) for lower extremity pain. RESULTS: Local expressions instead of CX3CL1 and CCL2 in STANR, AF, and NP were significantly higher in the SP group than in M-MP compared with scoliosis painless group. Expressions of both CX3CL1 and CCL2 in STANR and AF were positively correlated with VAS scores for lower extremity and for low back pain, respectively. In addition, CX3CL1 and CCL2 expressions in STANR were negatively associated with JOA scores. There were no significant differences of serum CX3CL1 and CCL2 levels among SP group, M-MP group, and scoliosis painless group. CONCLUSION: Both CX3CL1 and CCL2 may play important roles in maintaining pain in LDH patients. Local blockade of CX3CL1 and CCL2 in LDH patients with persistent pain deserves further intensive study.
RESUMEN
BACKGROUND: Uncontrol cell growth and proliferation is acknowledged to responsible for cancer-related deaths by disorganizing the balance of growth promotion and growth limitation. Aberrant expression of microRNA play essential roles in cancer development, leads to cell proliferation, growth and survival, and promotes the development of various human tumors, including osteosarcoma. Elucidating the molecular mechanism of this abnormality in osteosarcoma carcinogenesis may improve diagnostic and therapeutic strategies for this malignancy. METHODS: The expression of miR-664 in osteosarcoma cell lines and osteosarcoma tissues was examined using real-time PCR. The effects of miR-664 on osteosarcoma cell proliferation were evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, colony formation and Anchorage-independent growth ability assay. The effect of miR-664 on FOXO4 was determine by luciferase assays and western blot assay. RESULTS: The expression of miR-664 was markedly upregulated in osteosarcoma cell lines and tissues, and upregulation of miR-664 enhanced, whereas downregulation of miR-664 inhibited the proliferation of osteosarcoma cells in vivo. Furthermore, using bioinformatics and biological approaches, we showed that miR-664 directly targeted and suppressed the expression of tumor suppressors FOXO4. CONCLUSIONS: Our findings suggest that miR-664 functions as an oncogene miRNA and has an important role in promoting human osteosarcoma cell proliferation by suppressing FOXO4 expression. These data suggests that miR-664 may represent a novel therapeutic target of microRNA-mediated suppression of cell proliferation in osteosarcoma.