ABSTRACT
Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Up-regulation of miR-124 inhibits invasion and proliferation of prostate cancer cells through mediating JAK-STAT3 signaling pathway, by Z. Wu, W. Huang, B. Chen, P.-D. Bai, X.-G. Wang, J.-C. Xing, published in Eur Rev Med Pharmacol Sci 2017; 21 (10): 2338-2345-PMID: 28617558" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/12802.
ABSTRACT
OBJECTIVE: Signal transducer and activator of transcription 3 (STAT3) is an important protein in Janus kinase (JAK)-STAT signaling pathway, and can facilitate expression of Bcl-2 and Cyclin D1 gene, thus playing a role in tumor pathogenesis. Bioinformatics analysis revealed targeted binding sites between mircroRNA-124 (miR-124) and 3'-UTR of STAT3 mRNA. This study aims to investigate the role of miR-124 in regulating STAT3 expression and proliferation, cycle, apoptosis and invasion of prostate cancer cells. MATERIALS AND METHODS: Dual luciferase reporter gene assay demonstrated targeted correlation between miR-124 and STAT3. Expression of miR-124, STAT3, p-STAT3, Bcl-2 and Cyclin D1 was compared between normal human prostate epithelial cell RWPE-1 and prostate cancer cell DU145. In vitro cultured DU145 cells were treated with miR-124 mimic and/or si-STAT3, to compare expression of STAT3, phosphorylated STAT3 (p-STAT3), B-cell lymphoma-2 (Bcl-2) and Cyclin D1. Flow cytometry detected cell apoptosis and cycle, followed by clonal formation and transwell assay to test malignant proliferation and cell invasion. RESULTS: Targeted regulation existed between miR-124 and STAT3. Comparing to RWPE-1, DU145 cells had lower miR-124 expression, G0/G1 phase ratio, or cell apoptosis, plus higher expression of STAT3, p-STAT3, Bcl-2 and Cyclin D1, ratio of S or G2/M phase. Transfection of miR-124 mimic and/or si-STAT3 remarkably decreased gene expression, weakened clonal formation, cell invasion, ratio of S and G2/M phase, cell apoptosis and increased G0/G1 ratio. CONCLUSIONS: MiR-124 up-regulation significantly suppresses STAT3, pSTAT3 and downstream Bcl-2 and Cyclin D1 expression, weakens cell invasion or malignant proliferation potency, induces G0/G1 phase arrest, and facilitates cell apoptosis.
Subject(s)
Cell Proliferation/genetics , Janus Kinase 3/metabolism , MicroRNAs/genetics , Prostatic Neoplasms/metabolism , STAT3 Transcription Factor/metabolism , Apoptosis/genetics , Cell Line, Tumor , Humans , Male , Neoplasm Invasiveness , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Signal Transduction/genetics , Transcriptional Activation , Up-RegulationABSTRACT
INTRODUCTION: To assess the risk factors of Gleason sum upgrading between biopsy and radical prostatectomy (RP) and update the nomogram for the prediction of Gleason sum upgrading. METHODS: The study cohort consisted of 237 Chinese prostate adenocarcinoma patients who underwent 10-core prostate biopsy and subsequently received RP in Huashan Hospital from February 2011 to May 2015. The main outcome of our study was Gleason sum upgrading between biopsy and RP pathology. Univariate and multivariate logistic regression models were conducted to explore the potential predictors, and ultimately to build the nomograms. The prediction model was further evaluated for its ability to predict significant upgrading in patients with biopsy Gleason sum<8. RESULTS: In the main cohort of all the patients, Gleason sum upgrading was observed in 62 (26.16%) patients. The pre-operative prostate-specific antigen (PSA) level, biopsy Gleason sum, and digital rectal examination were used in building the nomogram, which was validated internally with a bootstrap-corrected concordance index of 0.787. In the sub-cohort of 115 patients with standardized biopsy details, Gleason sum upgrading was observed in 31 (26.96%) patients. The pre-operative PSA level, biopsy Gleason sum, and number of positive cores were used in the nomogram, which was also validated internally with a bootstrap-corrected concordance index of 0.833. These two nomograms both demonstrated satisfactory statistical performance for predicting significant upgrading. CONCLUSIONS: Updated nomograms to predict Gleason sum upgrading in Chinese population between biopsy and RP were developed, demonstrating good statistical performance upon internal validation.