ASPM overexpression enhances cellular proliferation and migration and predicts worse prognosis for papillary renal cell carcinoma.

Various studies have recognized the vital role of the abnormal spindle microtubule assembly (ASPM) gene in the progression of numerous tumors and its association with their poorer clinical outcomes. Nonetheless, the clinical significance and regulatory mechanism of ASPM in papillary renal cell carcinoma (PRCC) have not been illuminated. Herein, we designed a series of experiments to determine the functional significance of ASPM in PRCC. The expression of ASPM was significantly elevated in PRCC tissues and cells, and a higher expression level of ASPM was associated with poor clinical outcomes in patients with PRCC. Following the knockdown of ASPM, the proliferation, invasion, and migration abilities of PRCC cells were all repressed. Moreover, the silencing of ASPM attenuated the expressions of crucial proteins involved in Wnt/b-catenin signaling pathway, including Dvl-2, ß-catenin, TCF4, and LEF1. Our study shows the biological significance of ASPM in PRCC and provides new insights for exploring therapeutic targets in PRCC.

Biological functions of miR-363-3p/BTG2 in the metastasis of bladder cancer.

PURPOSE: This study aimed to detect the differential expression of microRNA-363-3p (miR-363-3p) in bladder cancer (BC) samples and to explore its influence on metastasis of BC cells. METHODS: Expression level of miR-363-3p in 70 cases of BC tissues and paracancerous tissues was detected. After establishing miR-363-3p overexpression model in 253j and RT4 cells, their migratory ability was assessed by Transwell and wound healing assay. The interaction between miR-363-3p and its downstream gene was predicted online and further confirmed by luciferase assay. Their involvement in regulating metastasis of BC cells was finally explored. RESULTS: MiR-363-3p was downregulated in BC tissues compared with that in the paracancerous tissues. Overexpression of miR-363-3p markedly weakened migratory ability in BC cells. BTG2 was the downstream gene binding miR-363-3p. In addition, overexpression of BTG2 reversed the inhibitory effect of miR-363-3p on BC cell migration. CONCLUSIONS: MiR-363-3p is lowly expressed in BC samples. It weakens in vitro migratory ability in BC cells through downregulating BTG2.

A novel long non-coding RNA-based prognostic signature for renal cell carcinoma patients with stage IV and histological grade G4.

This study aimed to establish a lncRNA-based signature for predicting the prognosis of patients with high stage and grade renal cell carcinoma (RCC). According to the Surveillance, Epidemiology, and End Results (SEER) database, sex, age, grade, stage, surgery, chemotherapy, radiation, tumor size, and marital status were the independent prognostic factors for RCC and also had significant correlations with the overall survival through Cox univariate and multivariate analyses. Noticeably, among these influencing factors, the histological classification of undifferentiated group and pathological stage IV had the greatest prognostic risks for RCC patients. Furthermore, based on the samples at stage IV and histological grade G4 from The Cancer Genome Atlas (TCGA) portal, 9 key lncRNAs, including KIAA2012, CCNT2-AS1, ITPKB-AS1, TBX2-AS1, NUTM2A-AS1, LINC02522, LINC02384, LINC01559, and LINC00865 were identified and a prognostic signature was constructed by Lasso analysis and Cox regression model. The Kaplan-Meier analysis suggested that patients at stage IV and histological grade of G4 in high risk score group had a worse overall survival than that in low risk score group. The following receiver operating characteristic curve (ROC) curves also showed that this signature possesses a better predictive power performance. Pathway enrichment analysis discovered that 9 lncRNAs held potential roles in cell division, cell cycle, DNA damage and cytokines levels in RCC. This work indicates that the established 9-lncRNA signature has a good capacity in predicting the prognosis of RCC patients with stage IV and histological grade of G4, and may be helpful for guiding the treatment strategies for RCC patients.

Potential role of the compound Eucommia bone tonic granules in patients with osteoarthritis and osteonecrosis: A retrospective study.

BACKGROUND: Osteoarthritis is a major source of pain, disability, and socioeconomic cost worldwide. Osteonecrosis is a disabling disorder that frequently occurs in the younger population aged from 20-50 years. The compound Eucommia bone tonic granules, a traditional Chinese medicine, can alleviate the damage of osteoarthritis and osteonecrosis. AIM: To investigate the potential role of the compound Eucommia bone tonic granules (Eucommia) in the treatment of patients with osteoarthritis and osteonecrosis. METHODS: One-hundred forty osteoarthritis and osteonecrosis cases admitted to our hospital from January 2013 to December 2017 were selected. Patients were divided into two groups: Eucommia-meloxicam group and meloxicam group. Clinical efficacy and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score were evaluated according to the evaluation criteria of orthopedic diseases. The levels of bone-GLA protein, interleukin-17, recombinant human S100 calcium binding protein A12, sphingosine 1-phosphate, cystatin C, creatinine, and hemoglobin in peripheral blood were determined. RESULTS: The total effective rate in the two osteoarthritis groups was not different, but the total effective rate in the two osteonecrosis groups was significantly different. The overall efficacy of Eucommia-meloxicam group was superior to that of the meloxicam group. WOMAC showed that pain, stiffness, and dysfunction in the two groups of osteoarthritis and osteonecrosis before and after treatment were significantly different. The concentration of recombinant human S100 calcium binding protein A12, sphingosine 1-phosphate, cystatin C, creatinine, and hemoglobin before and after treatment in the Eucommia-meloxicam group and meloxicam group of osteoarthritis and osteonecrosis were significantly different, and the two treatment groups were significantly different from each other for osteoarthritis. CONCLUSION: Our findings indicate that Eucommia can effectively enhance the curative effect of meloxicam, and the combination of Eucommia and meloxicam is superior to meloxicam alone.

A bladder cancer microenvironment simulation system based on a microfluidic co-culture model.

A tumor microenvironment may promote tumor metastasis and progression through the dynamic interplay between neoplastic cells and stromal cells. In this work, the most representative and significant stromal cells, fibroblasts, endothelial cells, and macrophages were used as vital component elements and combined with bladder cancer cells to construct a bladder cancer microenvironment simulation system. This is the first report to explore bladder cancer microenvironments based on 4 types of cells co-cultured simultaneously. This simulation system comprises perfusion equipment, matrigel channel units, a medium channel and four indirect contact culture chambers, allowing four types of cells to simultaneously interact through soluble biological factors and metabolites. With this system, bladder cancer cells (T24) with a tendency to form a 'reticular' structure under 3 dimensional culture conditions were observed in real time. The microenvironment characteristics of paracrine interactions and cell motility were successfully simulated in this system. The phenotype change process in stromal cells was successfully reproduced in this system by testing the macrophage effector molecule Arg-1. Arg-1 was highly expressed in the simulated tumor microenvironment group. To develop "precision medicine" in bladder cancer therapy, bladder cancer cells were treated with different clinical 'neo-adjuvant' chemotherapy schemes in this system, and their sensitivity differences were fully reflected. This work provides a preliminary foundation for neo-adjuvant chemotherapy in bladder cancer, a theoretical foundation for tumor microenvironment simulation and promotes individual therapy in bladder cancer patients.