ABSTRACT
Deregulation of tripartite motif (TRIM) family proteins contribute to multiple biological processes such as neurodegeneration, development, inflammation, cell survival, apoptosis, and carcinogenesis. However, the biological function and molecular mechanism of TRIM family proteins in osteosarcoma chemoresistance remain unclear. In the current study, we found the protein expression of TRIM10 was markedly overexpressed in cisplatin resistance's osteosarcoma tissues and TRIM10 overexpression was inversely correlated with osteosarcoma patient survival. Furthermore, overexpression of TRIM10 confers cisplatin resistance on osteosarcoma cells; however, repressing TRIM10 sensitized osteosarcoma cell lines to cisplatin cytotoxicity in vitro. Mechanically, TRIM10 upregulated the nuclear levels of p65, thereby activating canonical NF-κB signaling. Taken together, our results suggest that TRIM10 contributed to cisplatin resistance in osteosarcoma cells, and targeting the TRIM10/p65 axis may represent a promising strategy to enhance cisplatin response in osteosarcoma patients with chemoresistance.
Subject(s)
Carcinogenesis/genetics , Cisplatin/pharmacology , Drug Resistance, Neoplasm/genetics , Intracellular Signaling Peptides and Proteins/genetics , NF-kappa B/metabolism , Osteosarcoma/genetics , Signal Transduction , Tripartite Motif Proteins/genetics , Carcinogenesis/drug effects , Cell Line, Tumor , Disease Progression , Gene Expression Regulation, Neoplastic/drug effects , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Osteosarcoma/pathology , Prognosis , Signal Transduction/drug effects , Tripartite Motif Proteins/metabolism , Up-Regulation/drug effects , Up-Regulation/geneticsABSTRACT
OBJECTIVE: To evaluate the feasibility and safety of cervical kinematic MRI (KMRI) in patients with cervical spinal cord injury without fracture and dislocation (CSCIWFD). METHODS: This was a single-institution case-only study. Patients with CSCIWFD were enrolled in our institution from February 2015 to July 2019. Cervical radiography and CT were performed first to exclude cervical tumors, and major fracture or dislocation. Then neutral static and kinematic (flexion and extension) MRI was performed for patients who met the inclusion criteria under the supervision of a spinal surgeon. Any adverse events during the KMRI examination were recorded. Patients received surgical or conservative treatment based on the imaging results and patients' own wishes. The American Spinal Injury Association impairment scale (AIS) grade and the Japanese Orthopedic Association (JOA) score were evaluated on admission, before KMRI examination, and after KMRI examination. For the surgical patients, AIS grade and JOA score were evaluated again 1 week after the operation. The JOA scores were compared among different time points using the paired t-test. RESULTS: A total of 16 patients (12 men and 4 women, mean age: 51.1 [30-73] years) with CSCIWFD were included in the present study. Clinical symptoms included facial trauma, neck pain, paraplegia, paresthesia, hyperalgesia, sensory loss or weakness below the injury level, and dyskinesia. On admission, AIS grades were B for 2 cases, C for 5, and D for 9. A total of 14 patients underwent neutral, flexion, and extension cervical MRI examination; 2 patients underwent neutral and flexion examination because they could not maintain the position for a prolonged duration. No patient experienced deterioration of neurological function after the examinations. The AIS grades and JOA scores evaluated post-examination were similar to those evaluated pre-examination (P > 0.05) and significantly higher than those on admission (P < 0.05). A total of 12 patients received surgical treatment, 11 of whom underwent anterior cervical discectomy and interbody fusion and 1 underwent posterior C3/4 fusion with lateral mass screws. The remaining 4 patients were offered conservative therapy. None of the patients experienced any complications during the perioperative period. The AIS grade did not change in most surgical patients, except that 1 patient changed from grade C to D 1 week after the operation. The JOA score 1 week after surgery was significantly higher than those on admission and around examination for the surgical patients (P < 0.05). CONCLUSION: Cervical KMRI is a safe and useful technique for diagnosis of CSCIWFD, which is superior to static cervical MRI for therapeutic decision-making in patients with CSCIWFD.
