Search

Circular RNAs play crucial regulatory roles in the progression of various cancers. Nevertheless, the underlying mechanisms of circRNAs in prostate cancer (PCa) proliferation and metastasis remain largely uncertain. Here, we performed circRNA microarray analyses to identify differentially expressed circRNAs in a normal prostate epithelial cell line and PCa cell lines. We found that hsa_circ_0063329 was significantly downregulated in PCa. A series of in vitro and in vivo functional assays showed that overexpression of hsa_circ_0063329 inhibits PCa cell progression, while silencing of hsa_circ_0063329 achieved the opposite effects. Mechanistically, bioinformatics analysis, RNA pulldown, RNA-seq and dual-luciferase reporter assays demonstrated that hsa_circ_0063329 exerts its effect by sponging miR-605-5p to derepress TG-interacting factor 2 (TGIF2) and inactivate the TGF-β pathway. In conclusion, hsa_circ_0063329 inhibits the proliferation and metastasis of PCa via modulation of the miR-605-5p/TGIF2 axis, and targeting hsa_circ_0063329 may provide a promising treatment strategy for aggressive PCa. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) has become the most frequently occurring cancer among western men according to the latest report, and patients' prognosis is often poor in the event of tumor progression, therefore, many researches are devoted to exploring the molecular mechanism of PCa metastasis. MicroRNAs (miRNA) have proved to play an important role in this process. In present study, by combining clinical samples with public databases, we found that miR-629-5p increased to varying degrees in primary localized PCa tissues and metastatic PCa tissues compared with adjacent normal tissues, and bioinformatics analysis suggested that high level of miR-629-5p was related to poor prognosis. Functionally, miR-629-5p drove PCa cell proliferation, migration and invasion in vitro , and promoted growth of PCa cells in vivo. Moreover, A-kinase Anchor Protein 13 (AKAP13) was screened as a direct target of miR-629-5p, that expression was negatively correlated with the malignant phenotype of tumor cells. In the end, through verification in clinical specimens, we found that AKAP13 could be independently used as a clinical prognostic indicator. Overall, the present study indicates that miR-629-5p plays an oncogenic role in PCa by targeting AKAP13, which provides a new idea for clinical diagnosis and treatment of complex refractory PCa. [ABSTRACT FROM AUTHOR]

Snail is a dedicated transcriptional repressor and acts as a master inducer of EMT and metastasis, yet the underlying signaling cascades triggered by Snail still remain elusive. Here, we report that Snail promotes colorectal cancer (CRC) migration by preventing non‐coding RNA LOC113230‐mediated degradation of argininosuccinate synthase 1 (ASS1). LOC113230 is a novel Snail target gene, and Snail binds to the functional E‐boxes within its proximal promoter to repress its expression in response to TGF‐β induction. Ectopic expression of LOC113230 potently suppresses CRC cell growth, migration, and lung metastasis in xenograft experiments. Mechanistically, LOC113230 acts as a scaffold to facilitate recruiting LRPPRC and the TRAF2 E3 ubiquitin ligase to ASS1, resulting in enhanced ubiquitination and degradation of ASS1 and decreased arginine synthesis. Moreover, elevated ASS1 expression is essential for CRC growth and migration. Collectively, these findings suggest that TGF‐β and Snail promote arginine synthesis via inhibiting LOC113230‐mediated LRPPRC/TRAF2/ASS1 complex assembly and this complex can serve as potential target for the development of new therapeutic approaches to treat CRC. SYNOPSIS: Non‐coding RNA LOC113230 is a tumor suppressor of CRC cells by acting as a scaffold to faciliate the assembly of the LRPPRC/TRAF2 E3 complex to ubiquitinate and degrade ASS1 and inhibit arginine synthesis. The LRPPRC/TRAF2/ASS1 complex can serve as potential target for the development of new therapeutic approaches to treat CRC. Snail directly binds the E‐boxes within the promoter region to repress LOC113230 in CRC cells in response to TGF‐β induction.LOC113230 suppresses CRC cell growth and metastasis.LOC113230 inhibits arginine synthesis by recruiting a complex composed of the TRAF2 ubiquitin ligase and LRPPRC to ubiquitinate and degrade ASS1. [ABSTRACT FROM AUTHOR]

Background: The investigation of underlying mechanism and the exploitation of novel therapies for metastatic prostate cancer (PCa) are still urgently needed. miR-199b-5p has been suggested to function as tumour suppressor in various human cancers. However, the clinical significance and role of miR-199b-5p in PCa remain unclear.Methods: The current study sought to investigate the expression status of miR-199b-5p in PCa and the involved molecular mechanisms in PCa metastasis by using bioinformatics analyses, loss-and gain-of-functions and rescue experiments in vitro and in vivo.Results: We demonstrated that miR-199b-5p was significantly downregulated in metastatic PCa tissues and cells when compared with the normal prostate tissue, the localised disease, the weakly metastatic and androgen-dependent PCa cell and the normal prostate epithelial cell. We also found that miR-199b-5p drastically suppressed PCa cell proliferation, migration and invasion in vitro and inhibited xenografts tumour growth and metastasis in vivo. Mechanistically, our results showed that miR-199b-5p could inhibit discoidin domain receptor tyrosine kinase 1 (DDR1) expression by directly targeting its 3'-UTR, thereby hindering epithelial-mesenchymal transition (EMT)-associated traits, which were induced by DDR1 activating ERK signalling pathway. Moreover, PCa patients with low miR-199b-5p expression level had a remarkably shorter overall survival than those with high miR-199b-5p level, indicating an association of miR-199b-5p loss with poor prognosis in patients with PCa. Furthermore, DDR1 was upregulated in PCa, and significantly correlated with high Gleason score, advanced pathological stage, tumour metastasis and shorter overall survival.Conclusions: Our study, for the first time, provide evidence of a tumour-suppressive function of miR-199b-5p in the invasion and metastasis of PCa, supporting the translational exploitation of miR-199b-5p-based therapeutic approaches for PCa metastases. Also, the miR-199b-5p-DDR1-ERK signalling axis identified in this study represents a novel mechanism of regulating EMT in PCa metastases. [ABSTRACT FROM AUTHOR]

The prostate stem cell antigen (PSCA), as a predominantly prostate-specific marker, is overexpressed in most prostate cancer specimens, is positively correlated with prostate cancer androgen independence, and has the potential to be treated with castration-resistant prostate cancer (CRPC) as a gene therapy target. Using the typical androgen deprivation therapy, most tumors will progress to CRPC, as well as develop into neuroendocrine prostate cancer (NEPC) characterized by the expression of neuroendocrine markers such as enolase 2 (NSE). Our study was aimed at investigating the expressions of PSCA and NSE and the relationship between the two markers, as well as the correlation between the PSCA and NSE expressions and the clinicopathological parameters in prostate cancer specimens from 118 patients by using immunohistochemistry. Our results demonstrated that the PSCA and NSE protein expressions did not correlate with the prostate cancer patients' age or the hormone therapy but showed a significant correlation with the pathological tumor stage of prostate cancer, the Gleason score, and the presence of metastasis. There is a positive association between PSCA and NSE but a negative one between the prostate-specific antigen (PSA) and PSCA or between PSA and NSE. High PSCA and NSE expressions correlated with a poor prognosis in prostate cancer patients. PSCA may play an important role in the progression of neuroendocrine prostate cancer (NEPC). [ABSTRACT FROM AUTHOR]

Prostate adenocarcinoma (PCa) is the most common cause of death due to malignancy among men, and bone metastasis is the leading cause of mortality in patients with PCa. Therefore, identifying the causes and molecular mechanism of bone metastasis is important for early detection, diagnosis and personalized therapy. In this study, we systematically analyzed molecular correlates of bone metastasis by bioinformatics analysis. A total of 12 differentially expressed microRNAs (miRNAs) and 102 differentially expressed genes were identified. Five miRNAs had prognostic significance in biochemical recurrence‐free survival (miR‐636, miR‐491‐5p, miR‐199b‐5p, miR‐199b‐3p, miR‐28‐3p). The differentially expressed genes were significantly enriched in extracellular matrix, cell‐substrate adhesion, collagen and integrin. Seven hub genes (VCAN, COL3A1, COL1A1, APOE, COL1A2, SDC1, THY1) with worse biochemical recurrence‐free survival and one hub gene (MMP9) with worse overall survival were detected. miR‐636, a novel oncogene, was found to be up‐regulated in bone metastatic PCa tissues and also predominately up‐regulated in human PCa cell lines. miR‐636 promoted cellular invasion and migration, and may promote bone metastasis via targeting MBNL2, TNS1 and STAB1. In conclusion, we have successfully defined molecular signatures of bone metastasis in PCa. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the value of nodal grouping (NG), defined as the presence of at least three contiguous lymph nodes (LNs) within one LN region, in staging and management of patients with non-metastatic nasopharyngeal carcinoma (NPC).Methods: MR images were reviewed to evaluate LN variables, including NG. The Kaplan-Meier method and multivariate Cox regression models evaluated the association between the variables and survival. Harrell's concordance index (C-index) was used to measure the performance of prognostic models. The outcome of induction chemotherapy (IC) in patients with and without NG was compared using matched-pair analysis.Results: In 1224 patients enrolled, NG was found to be an independent prognostic factor for overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and regional recurrence-free survival. The hazard ratio and 95% confidence interval (CI) of NG for OS (3.86, 2.09-7.12) were higher than those of stage N2 (3.54, 1.89-6.70). On upgrading patients with NG from stages N1 to N2, the revised N staging yielded a higher C-index compared to the American Joint Committee on Cancer system in predicting PFS (0.664 vs. 0.658, p = 0.022) and DMFS (0.699 vs. 0.690, p = 0.005). Results of the matched-pair analysis revealed that for patients with NG in stages N1 and N2, IC was correlated with improved OS (p = 0.022), PFS (p = 0.007), and DMFS (p = 0.021).Conclusions: NG is a significant prognostic factor for patients with NPC. Patients with NG may be upgraded from stages N1 to N2. NG was also a marker for identifying patients who would benefit from IC.Key Points: • Nodal grouping, defined as the presence of at least three contiguous LNs within one LN region on MRI, was identified as a significant prognostic factor. • In patients with nasopharyngeal carcinoma, nodal grouping may influence lymph node staging. • Nodal grouping was a marker for identifying patients who may benefit from induction chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the third most prevalent cancer type and the third leading cause of cancer-related deaths worldwide, it is urgently needed to discover a new marker for the progress of CRC. Many long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in CRC, and may be feasible as effective biomarkers and prognostic factors. The aim of this study was to identify the prognostic value of various lncRNAs in CRC. Methods: Pubmed, Web of Science, Embase and Cochrane Library were searched for potentially related studies. A total of 34 eligible studies including 30 on overall survival (OS), 7 on disease-free survival (DFS), 1 on relapse-free survival (RFS), 2 on disease-specific survival (DSS) and 29 on clinicopathological features were qualified from the databases. Results: The results showed that the expression levels of lncRNAs were significantly associated with poor OS (hazard ratio (HR) = 2.08, 95% confidence interval (CI) = 1.68–2.57, P<0.001, I2 = 70%), DFS (HR = 1.79, 95% CI = 1.54–2.08, P<0.001, I2 = 6%) and DSS (HR = 0.11, 95% CI = 0.02–0.54, P = 0.007, I2 = 14%). Subgroup analysis further showed that lncRNA transcription level was significantly associated with tumor differentiation (odds ratio (OR) = 0.51, 95% CI = 0.34–0.77, P = 0.001), lymph node metastasis (OR = 1.63, 95% CI = 1.23–2.17, P = 0.0007), distant metastasis (OR = 2.06, 95% CI = 1.29–3.30, P = 0.002), TNM stage (OR = 0.44, 95% CI = 0.32–0.62, P<0.001), tumor invasion depth (OR = 0.48, 95% CI = 0.39–0.60, P<0.001). Conclusions: The meta-analysis demonstrated that abnormal lncRNA transcription level may serve as a promising indicator for prognostic of patients with CRC. [ABSTRACT FROM AUTHOR]

p66α is a GATA zinc finger domain-containing transcription factor that has been shown to be essential for gene silencing by participating in the NuRD complex. Several studies have suggested that p66α is a risk gene for a wide spectrum of diseases such as diabetes, schizophrenia, and breast cancer; however, its biological role has not been defined. Here, we report that p66α functions as a tumor suppressor to inhibit breast cancer cell growth and migration, evidenced by the fact that the depletion of p66α results in accelerated tumor growth and migration of breast cancer cells. Mechanistically, immunoprecipitation assays identify p66α as a p53-interacting protein that binds the DNA-binding domain of p53 molecule predominantly via its CR2 domain. Depletion of p66α in multiple breast cells results in decreased expression of p53 target genes, while over-expression of p66α results in increased expression of these target genes. Moreover, p66α promotes the transactivity of p53 by enhancing p53 binding at target promoters. Together, these findings demonstrate that p66α is a tumor suppressor by functioning as a co-activator of p53. [ABSTRACT FROM AUTHOR]