Oncogenic gene TRIM10 confers resistance to cisplatin in osteosarcoma cells and activates the NF-κB signaling pathway.

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.

Dynamic evaluation of the cervical spine by kinematic MRI in patients with cervical spinal cord injury without fracture and dislocation.

BACKGROUND: The pattern of changes in the cervical spine and the spinal cord and their dynamic characteristics in patients with cervical spinal cord injury without fracture and dislocation remain unclear. This study aimed to evaluate the dynamic changes in the cervical spine and spinal cord from C2/3 to C7/T1 in different positions by using kinematic magnetic resonance imaging in patients with cervical spinal cord injury without fracture and dislocation. This study was approved by the ethics committee of Yuebei People's Hospital. METHODS: Using median sagittal T2-weighted images for 16 patients with cervical spinal cord injury without fracture and dislocation who underwent cervical kinematic MRI, the anterior space available for the cord, spinal cord diameter, posterior space available for the cord from C2/3 to C7/T1, and Muhle's grade were determined. The spinal canal diameter was calculated by adding the anterior space available for the cord, spinal cord diameter, and posterior space available for the cord. RESULTS: The anterior space available for the cord, posterior space available for the cord, and spinal canal diameters at C2/3 and C7/T1 were significantly higher than those from C3/4 to C6/7. Muhle's grades at C2/3 and C7/T1 were significantly lower than those at the other levels. Spinal canal diameter was lower in extension than in the neutral and flexion positions. In the operated segments, significantly lesser space was available for the cord (anterior space available for the cord + posterior space available for the cord), and the spinal cord diameter/spinal canal diameter ratio was higher than those in the C2/3, C7/T1, and non-operated segments. CONCLUSION: Kinematic MRI demonstrated dynamic pathoanatomical changes, such as canal stenosis in different positions, in patients with cervical spinal cord injury without fracture and dislocation. The injured segment had a small canal diameter, high Muhle's grade, low space available for the cord, and high spinal cord diameter/spinal canal diameter ratio.

High expression of small nucleolar RNA host gene 3 predicts poor prognosis and promotes bone metastasis in prostate cancer by activating transforming growth factor-beta signaling.

Bone metastasis is closely related to tumor death in prostate cancer (PC). Long noncoding RNA small nucleolar RNA host gene 3 (SNHG3) has been implicated in the initiation and progression of multiple human cancers. Nevertheless, the biological function of SNHG3 in PC has not been elucidated. Our results indicated that SNHG3 was upregulated in bone metastasis-positive PC tissues compared to bone metastasis-negative PC tissues and adjacent normal tissues. High expression of SNHG3 indicates advanced clinicopathological features and predicts poor prognosis in patients with PC. Meanwhile, SNHG3 knockdown suppressed the proliferation, migration, and invasion abilities of PC cells and inhibited PC cell metastasis to the bone. Mechanistically, SNHG3 enhanced the expression of transforming growth factor beta receptor 1 (TGFBR1) and activated transforming growth factor-Beta (TGF-ß) signaling by targeting miR-214-3p. Our study demonstrated the novel role of the SNHG3/miR-214-3p/TGF-ß axis in tumor growth and bone metastasis in PC, indicating that SNHG3 may act as a biomarker and promising therapeutic target against PC.

Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p.

Long noncoding RNAs have been demonstrated to play crucial roles in the pathogenesis of spinal cord injury (SCI). In this study, we aimed to explore the roles and underlying mechanisms of lncRNA X-inactive specific transcript (XIST) in SCI progression. SCI mice model was constructed and evaluated by the Basso-Beattie-Bresnahan method. The SCI cell model was constructed by treating BV2 cells with lipopolysaccharide (LPS). The levels of XIST and miR-219-5p were determined by the reverse transcription quantitative polymerase chain reaction. The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Protein levels were measured via western blot assay. Cell viability and apoptosis were evaluated by cell counting kit-8 assay and flow cytometry analysis, respectively. The relationship between XIST and miR-219-5p was analyzed by online tool starBase, dual-luciferase reporter assay, and RNA immunoprecipitation assay. As a result, the XIST level was enhanced and the miR-219-5p level was declined in the SCI mice model. XIST was also upregulated in LPS-induced BV2 cells. LPS treatment restrained BV2 cell viability and accelerated apoptosis and inflammatory response. XIST knockdown effectively weakened LPS-induced BV2 cell injury. miR-219-5p was identified as a target of XIST. Moreover, inhibition of miR-219-5p restored the impacts of XIST knockdown on cell viability, apoptosis, and inflammation in LPS-treated BV2 cells. In addition, LPS-induced XIST promoted the activation of the nuclear factor-κB (NF-κB) pathway by sponging miR-219-5p. In conclusion, XIST silencing promoted microglial cell viability and repressed apoptosis and inflammation by sponging miR-219-5p, thus promoting the recovery of SCI.

Feasibility and Safety of Cervical Kinematic Magnetic Resonance Imaging in Patients with Cervical Spinal Cord Injury without Fracture and Dislocation.

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.