In recent years, the NOTCH signaling pathway has been gradually studied in human malignancies. Inactivation of the NOTCH signaling pathway was uncovered to be correlated with the carcinogenesis of bladder cancer (BCa). Nevertheless, the specific molecular mechanism of NOTCH1 (one of the core factors of the NOTCH signaling pathway) is not well elucidated in BCa. This study focused on the mechanism by which NOTCH1 affects the biological behaviors of BCa cells. According to the experimental results of quantitative real‐time polymerase chain reaction, NOTCH1 was dysregulated in BCa tissues and cell lines. The prognostic value of NOTCH1 for the patients with BCa was determined using the Kaplan‐Meier method. Mechanism investigations revealed that NOTCH1 is a target of miR‐34c‐5p in BCa. Furthermore, microarray analysis was used to find the dysregulated long noncoding RNAs (lncRNA), which can bind with miR‐34c‐5p. Mechanism experiments further demonstrated the rationality of the HCG18‐miR‐34c‐5p‐NOTCH1 pathway. Functional assays were then applied to validate the inhibitory influences of NOTCH1 on the proliferation and migration of BCa cells. Furthermore, the inhibitory effects of NOTCH1 could be affected by miR‐34c‐5p or lncRNA HCG18. All findings in this study revealed that NOTCH1 suppresses the BCa progression by cooperating with lncRNA HCG18 and miR‐34c‐5p.
Incomplete understanding remains in the molecular mechanisms underlying progression and metastasis of renal cancer. The transcription factor SOX4 is upregulated in various human malignancies, including renal cancer, indicating it may be involved in renal tumorigenesis. In this study, we explored this hypothesis by loss-of-function and gain-of-function assays of SOX4 in renal cancer cell lines and renal epithelial cell line. We found that specific knockdown of SOX4 in renal cancer cell lines significantly suppressed the migration and invasion of cancer cells; specific overexpression of SOX4 in renal epithelial cell line markedly promoted the migration and invasion of the cell line. Epithelial-mesenchymal transition (EMT), a fundamental morphogenesis process, is implicated in renal cancer progression and metastasis. Our results demonstrated that SOX4 positively regulated the expression of mesenchymal cell markers and negatively regulated the expression of epithelial cell marker, and was involved in signal transduction pathway of TGFβ-induced EMT. In addition, SOX4 induced EMT probably through modulating the AKT/p-AKT signaling cascade. Finally, we found that SOX4 was significantly upregulated in clinical renal cancer samples compared with corresponding normal tissues and associated with EMT process in clinical samples. Taken together, our findings confirm a crucial function of SOX4 in the metastasis of renal cancer through orchestrating EMT and establish that the function suppression of SOX4-AKT-EMT axis might be an attractive therapeutic intervention during renal cancer metastasis.
To evaluate the safety and efficacy of laparoscopic bladder muscle flap reconstruction in the treatment of extensive ureteral avulsion.
Patients with full-length (re length > 20 cm) and upper ureteral (avulsion length > 10 cm) defects were eligible. All patients were treated with laparoscopic bladder muscle flap reconstruction. Peri-operative information and post-operative complications were recorded. The kidney function, urinary ultrasound or computed tomography (CT), sun-renal function tests emission computed tomography (ECT) and cystography after operation were recorded. Ten patients were included (7 with full-length and 3 with upper ureteral defects). Median age was 56 years and 70% of them were female. The average operation time and blood loss was 124 min and 92.2 ml. There was no treatment-related adverse effects including urinary leakage, renal colic, fever, etc. The median follow-up was 18.5 months (3–39 months). The surgery did not significantly alter the renal function and separation degree of the renal pelvis during long-term follow-up. Double J stents were removed in nine patients (90%) within six months after operation. Only one case was diagnosed with post-operative anastomotic stricture, and subsequently received laparoscopic ipsilateral nephrectomy one year after the reconstruction operation. All cases had normal voiding and pear-shaped cystography. Laparoscopic bladder flap repair is a safe and effective treatment approach together with several advantages for patients with full-length or upper ureteral avulsion.
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