The Influence of MDR1 Expression Regulated by miR-138 through TRPS1 Signaling Pathway on Multidrug Resistance of Osteosarcoma and Formation of Bacterial Infection Biofilm.

This study was to investigate the effect of microribonucleic acid (mi-RNA) on the resistance of human multidrug resistance gene 1 (MDR1) to osteosarcoma through the Trico-nasal finger syndrome 1 (TRPS1) pathway, as well as the effect of mi-RNA on biofilm formation. For this purpose, firstly, the expression of MDR1 and TRPS1 in osteosarcoma cells was detected by quantitative polymerase chain reaction (qPCR) technology. Moreover, the clinical paraffin sections of osteosarcoma cells were collected to explore the correlation between MDR1 and TRPS1. Then, both the MG-38 cells expressing and not expressing miR-138 were expanded. Afterward, a plasmid with a full-length clone of the TRPS1 antibody was applied to transfect the cells. Besides, Q-OCR was employed to detect the expression of TRPS1 and MDR1, and the expression of TRPS1 protein and P-glycoprotein (P-gp) was detected by Western blot (WB). The MTT method was adopted to detect the changes in the median lethal dose of doxorubicin and cisplatin in cells from each group. The well plate was used to establish an in vitro bacterial infection biofilm model, and the above two transfected cells were added during the model establishment process. Moreover, the formation of biofilm in the two groups was observed. The result of the paraffin biopsy was 33% (25/75) of mi-RNA, the positive rate of TRPS1 was 18.6%, and the Pearson correlation coefficient of the two was 0.477. Under mi-RNA interference, the TRPS1 and MDR1 of the three system cells were sharply reduced, and the trend of changes between the two was the same. The tolerance of the mi-RNA interference group to doxorubicin, cisplatin, paclitaxel and 5-fluorouracil decreased steeply, and the median lethal dose dropped, while the non-mi-RNA interference group showed the opposite trend. In addition, the number of colonies in the interference group was less sharp than that of the control group and the non-mi-RNA interference group. The conclusion was that mi-RNA could control the expression of MDR1 through the TRPS1 pathway, thus affecting the multi-drug resistance of osteosarcoma and also influencing the formation of bacterial biofilms.

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.

Validation of the Palliative Prognostic Index, Performance Status-Based Palliative Prognostic Index and Chinese Prognostic Scale in a home palliative care setting for patients with advanced cancer in China.

BACKGROUND: The predictive value of the prognostic tool for patients with advanced cancer is uncertain in mainland China, especially in the home-based palliative care (HPC) setting. This study aimed to compare the accuracy of the Palliative Prognostic Index (PPI), the Performance Status-Based Palliative Prognostic Index (PS-PPI), and the Chinese Prognosis Scale (ChPS) for patients with advanced cancer in the HPC setting in mainland China. METHODS: Patients with advanced cancer admitted to the hospice center of Yuebei People's Hospital between January 2014 and December 2018 were retrospectively calculated the scores according to the three prognostic tools. The Kaplan-Meier method was used to compare survival times among different risk groups. Receiver operating characteristic curve analysis was used to assess the predictive value. The accuracy of 21-, 42- and 90-day survival was compared among the three prognostic tools. RESULTS: A total of 1863 patients were included. Survival time among the risk groups of all prognostic tools was significantly different from each other except for the PPI. The AUROC of the ChPS was significantly higher than that of the PPI and PS-PPI for 7-, 14, 21-, 42-, 90-, 120-, 150- and 180-day survival (P < 0.05). The AUROC of the PPI and PS-PPI were not significantly different from each other (P > 0.05). CONCLUSIONS: The ChPS is more suitable than the PPI and PS-PPI for advanced cancer patients in the HPC setting. More researches are needed to verify the predictive value of the ChPS, PPI, and PS-PPI in the HPC setting in the future.

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.

Clinical evaluation of neoadjuvant chemotherapy for osteosarcoma.

PURPOSE: To evaluate the clinical efficacy of neoadjuvant chemotherapy for treating osteosarcoma. METHODS: 102 osteosarcoma patients in our hospital were randomly assigned into the neoadjuvant chemotherapy group and the surgery group. Patients in the chemotherapy group received neoadjuvant chemotherapy after pathological diagnosis. Surgery was performed 3 weeks after chemotherapy, followed by 4-6 cycles of postoperative chemotherapy. Osteosarcoma patients in the surgery group were operated once diagnosed and received no chemotherapy. Limb salvage or amputation surgery were performed according to the boundary of tumor resection. All patients were followed up for 24 months. The clinical efficacy, limb function, disease-free survival (DFS) and incidence of adverse events were compared between the two groups. RESULTS: Limb salvage rate and disease control survival in the chemotherapy group were higher than those of the surgery group (p<0.05). After follow up for 24 months, the 2-year DFS in the chemotherapy group was remarkably prolonged compared to the surgery group (p<0.05). No significant differences in the incidence of adverse events were observed between both groups (p>0.05). Limb function was markedly improved in the chemotherapy group compared with that of the surgery group. CONCLUSIONS: Preoperative neoadjuvant chemotherapy for treating osteosarcoma remarkably improves the limb salvage rate, disease control rate and overall survival (OS), and constitutes an effective and safe option for osteosarcoma patients.

Overexpression of TBL1XR1 confers tumorigenic capability and promotes recurrence of osteosarcoma.

Osteosarcoma is the most common malignant bone tumor in childhood and adolescence; however, the mechanism of this malignancy remains uncertain. Transducin (beta)-like 1 × -linked receptor 1 (TBL1XR1) plays an important role in controlling the transcriptional switch between gene activation and gene repression. However, the clinical significance and the precise biological function of TBL1XR1 in osteosarcoma remain unclear. In the present study, we revealed that TBL1XR1 is markedly upregulated in osteosarcoma cell lines and tissues, at both the mRNA and protein levels. Overexpression of TBL1XR1 dramatically enhanced, whereas inhibition of TBL1XR1 reduced, the cancer stem cell (CSC)-like phenotype and tumorigenicity of osteosarcoma cells, both in vitro and in vivo. Importantly, TBL1XR1 enhanced the tumorigenicity of osteosarcoma cells via activating STAT3 signaling and TBL1XR1 expression correlated significantly with STAT3 phosphorylation in osteosarcoma. Taken together, our results provide new evidence that TBL1XR1 overexpression induces CSCs-like phenotypes and tumorigenic capability of osteosarcoma and might represent a novel therapeutic target for its treatment.

Overexpression of miR-664 is associated with enhanced osteosarcoma cell migration and invasion ability via targeting SOX7.

Osteosarcoma (OS) is one of the most common types of primary sarcoma of bone in children and young adults, and the long-term prognosis for OS patients still remains dismal due to the lack of effective early diagnostic biomarkers. Identifying sensitive and specific biomarkers in carcinogenesis may improve diagnostic and therapeutic strategies for this malignancy. 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 migration and invasion were evaluated by cell invasion assays, migration assays, and three-dimension spheroid invasion assay. The effect of miR-664 on SOX7 was determined by luciferase assays and Western blot assay. The clinical association between miR-664 and SOX7 was analyzed by real-time PCR and Western blot assay. Expression of miR-664 was found to be upregulated in OS cell lines and tissues. Overexpression of miR-664 was associated with increased migration and invasive abilities of OS cells in vitro, whereas downregulation of miR-664 appeared to inhibit their migration and invasive potential. Furthermore, using biological approaches, we showed that miR-664 directly targeted and suppressed expression of the tumor suppressor SOX7. Additionally, the expression of miR-664 was negatively correlated with SOX7 expression in OS clinical tissues. Our findings suggest that miR-664 functions as an oncogene miRNA and has an important role in promoting human OS cell invasion and migration by suppressing SOX7 expression. Consequently, miR-664 may have potential as a novel diagnostic and therapeutic target of osteosarcoma.