RESUMEN
Osteosarcoma (OS) is a high-grade, aggressive bone sarcoma. LncRNAs play a key regulatory role in controlling biological and pathological processes. The expression of lncRNA SNHG9 varies among different cancer tissues, and the role of SNHG9 in OS progression is unclear. In this study, we found SNHG9 overexpression in OS tissues and cells. In addition, downregulated SNHG9 expression impaired the proliferation, migration, and invasion abilities of OS cells. SNHG9 expression was positively regulated by the transcription factor SOX4. SNHG9 interacted with miR-214-5p as a molecular sponge and SOX4 was identified as the target of miR-214-5p. The interaction affected the expression of SNHG9, miR-214-5p, and SOX4, and regulated OS cell proliferation, migration, and invasion. Therefore, the SNHG9/miR-214-5p/SOX4 feedback loop performs an important role in OS progression and might be used as a new potential therapeutic target for the treatment of OS.
Asunto(s)
Neoplasias Óseas , MicroARNs , Osteosarcoma , ARN Largo no Codificante , Apoptosis/genética , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Retroalimentación , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/metabolismo , Osteosarcoma/genética , Osteosarcoma/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factores de Transcripción SOXC/genética , Factores de Transcripción/genéticaRESUMEN
Apoptosis is reduced in the synovial tissue of patients with rheumatoid arthritis (RA), possibly due to decreased expression of pro-apoptotic genes. Programmed Cell Death 5 (PDCD5) has been recently identified as a protein that mediates apoptosis. Although PDCD5 is down-regulated in many human tumors, the role of PDCD5 in RA has not been investigated. Here we report that reduced levels of PDCD5 mRNA and protein are detected in RA synovial tissue (ST) and fibroblast-like synoviocytes (FLS) than in tissue and cells from patients with osteoarthritis (OA). We also report differences in the PDCD5 expression pattern in tissues from patients with these two types of arthritis. PDCD5 showed a scattered pattern in rheumatoid synovium compared with OA, in which the protein labeling was stronger in the synovial lining layer than in the sublining. We also observed increased expression and nuclear translocation of PDCD5 in RA patient-derived FLS undergoing apoptosis. Finally, overexpression of PDCD5 led to enhanced apoptosis and activation of caspase-3 in triptolide-treated FLS. We propose that PDCD5 may be involved in the pathogenesis of RA. These data also suggest that PDCD5 may serve as a therapeutic target to enhance sensitivity to antirheumatic drug-induced apoptosis in RA.