Long non-coding RNA LINC01207 promotes prostate cancer progression by downregulating microRNA-1972 and upregulating LIM and SH3 protein 1.

Prostate cancer is a heritable and clinically heterogeneous cancer. Both long non-coding RNAs (lncRNAs) and microRNAs (miRs) have been implicated in the pathogenesis and development of prostate cancer. Analysis of microarray data indicated that the lncRNA LINC01207 was differentially expressed in prostate cancer. In silico analysis predicted the interaction between LINC01207 and miR-1972 as well as the interaction between miR-1972 and the mRNAs LIM and SH3 protein 1 (LASP1). Thus, we explored the role of LINC01207 and miR-1972 in the growth and progression of prostate cancer. Quantitative real-time polymerase chain reaction revealed that LINC01207 and LASP1 were highly expressed in prostate cancer, while miR-1972 expression was lower. The interaction among LINC01207, miR-1972, and LASP1 was confirmed by RNA-fluorescence in situ hybridization, RNA immunoprecipitation, and dual luciferase reporter assay, which verified that LINC01207 could bind to miR-1972 and downregulate miR-1972, and miR-1972 targeted LASP1 and negatively regulated its expression. Both in vitro and in vivo experiments found that silencing LINC01207 inhibited cell proliferation, migration, invasion and tumor formation and enhanced apoptosis in prostate cancer cells, suggesting that LINC01207 functioned as a tumor promoter in prostate cancer and that it may represent a novel therapeutic target.

DDX11-AS1exacerbates bladder cancer progression by enhancing CDK6 expression via suppressing miR-499b-5p.

PURPOSE: We investigated DDX11-AS1 effects on bladder cancer (BLCA) progression to identify a new potential therapeutic target for BLCA. METHODS: BLCA cases (n = 108) were enrolled. SW780 and J82 cells were transfected. Cell counting kit-8 (CCK-8) assay, wound healing assay and transwell migration assay was conducted. Cell cycle and apoptosis was detected by flow cytometry. Luciferase reporter assay was performed. DDX11-AS1, miR-499b-5p and CDK6 mRNA expression in tissues/cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). In vivo experiment was performed using nude mice. CDK6 and Ki67 proteins expression in cells and xenograft tumors were researched by Western blot and immunohistochemistry. RESULTS: Overexpressed DDX11-AS1 in BLCA was associated with poor outcome of patients. Compared with siCtrl group, SW780 and J82 cells of siDDX11-AS1 group had lower OD450 value (P < 0.01), less cells in S phase, more apoptosis cells (P < 0.05), higher relative wound width (P < 0.05) and less invasive cell number (P < 0.01). DDX11-AS1 promoted CDK6 expression via inhibiting miR-499b-5p. Compared with oe-DDX11-AS1 group, SW780 cells of oe-DDX11-AS1 + miR-499b-5p mimic group and oe-DDX11-AS1 + siCDK6 group had lower OD450 value (P < 0.01), less cells in S phrase, more apoptosis cells (P < 0.01), higher relative wound width (P < 0.05) and less invasive cell numbers (P < 0.01). DDX11-AS1 knockdown inhibited SW780 cells growth in vivo and suppressed CDK6 and Ki67 expression in xenograft tumors. CONCLUSION: DDX11-AS1 exacerbates BLCA progression by enhancing CDK6 expression via suppressing miR-499b-5p.

Mass spectrometric detection combined with bioinformatic analysis identified possible protein markers and key pathways associated with bladder cancer.

We aimed to find possible protein markers and key pathways related to bladder cancer. In total, we extracted three bladder cancer tissues and three paracancerous tissues from Jiangsu Provincial People's Hospital Urology Department, and performed mass spectrometric detection with Q Exactive. Subsequently, we screened the differentially expressed proteins in the disease group and the normal group using the LIMMA package, and performed functional enrichment analyses using DAVID. Further, we constructed protein-protein interaction (PPI) networks with Cytoscape software, and analyzed modules with ClusterONE. In total, 165 differentially expressed proteins including 19 upregulated and 146 downregulated ones were obtained. ACTA2 (Actin, Alpha 2, Smooth Muscle, Aorta), ACTN1 (Actinin, Alpha 1), and VCL (Vinculin) were significant nodes with higher degrees in the PPI network. These three nodes were also hub nodes in module 2. Besides, functional enrichment analysis suggested that ECM-receptor interaction and focal adhesion were significant pathways, and these two pathways were also enriched in three network modules. In addition, ACTN1 and VCL were enriched in the focal adhesion pathway in module 2. Thus, ACTA2, ACTN1, and VCL may play important roles in bladder cancer progression and may be protein markers for this disease. The ECM-receptor interaction pathway and the focal adhesion pathway may be involved in the progression of bladder cancer. Furthermore, ACTN1 and VCL may play roles in bladder cancer development, partly via the focal adhesion pathway.

Inhibitory member of the apoptosis-stimulating protein of p53 is overexpressed in bladder cancer and correlated to its progression.

Several lines of direct evidence show that inhibitory member of the apoptosis-stimulating protein of p53 (iASPP) has an important function in cancer progression. However, its expression pattern and relationship with clinical pathologic characteristics in bladder cancer (BC) have not been completely elucidated. In this study, firstly, samples from 3 patients with invasive BC were detected by liquid chromatography tandem mass spectrometry to confirm overexpression of iASPP in BC, then samples from patients with noninvasive and invasive BC were detected by real-time polymerase chain reaction, Western blot, and tissue microarry immunohistochemistry. The relationship between iASPP expression and various clinicopathological features was investigated. The results showed m-RNA and protein of iASPP were overexpressed in BC and the rate of iASPP-positive cells was positively correlated with Union for International Cancer Control-Tumor, Node, Metastases stage, histologic grade, lymph node metastasis and poor overall survive. The data demonstrate that iASPP is overexpressed in BC and promotes the malignancy of BC. iASPP maybe serve as a potential therapeutic target for BC.

Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network.

High-throughput methods have been used to explore the mechanisms by which androgen-sensitive prostate cancer (ASPC) develops into castration-resistant prostate cancer (CRPC). However, it is difficult to interpret cryptic results by routine experimental methods. In this study, we performed systematic and integrative analysis to detect key miRNAs that contribute to CRPC development. From three DNA microarray datasets, we retrieved 11 outlier microRNAs (miRNAs) that had expression discrepancies between ASPC and CRPC using a specific algorithm. Two of the miRNAs (miR-125b and miR-124) have previously been shown to be related to CRPC. Seven out of the other nine miRNAs were confirmed by quantitative PCR (Q-PCR) analysis. MiR-210, miR-218, miR-346, miR-197, and miR-149 were found to be over-expressed, while miR-122, miR-145, and let-7b were under-expressed in CRPC cell lines. GO and KEGG pathway analyses revealed that miR-218, miR-197, miR-145, miR-122, and let-7b, along with their target genes, were found to be involved in the PI3K and AKT3 signaling network, which is known to contribute to CRPC development. We then chose five miRNAs to verify the accuracy of the analysis. The target genes of each miRNA were altered significantly upon transfection of specific miRNA mimics in the C4-2 CRPC cell line, which was consistent with our pathway analysis results. Finally, we hypothesized that miR-218, miR-145, miR-197, miR-149, miR-122, and let-7b may contribute to the development of CRPC through the influence of Ras, Rho proteins, and the SCF complex. Further investigation is needed to verify the functions of the identified novel pathways in CRPC development.

[Clinical research of genetic counseling].

To supply reliable materials for the assessment of recurrence risk,prenatal diagnosis and the supervision of high risk persons,we analyzed 10811 patients with the methods of cytogenetics,fluorescent in situ hybridization and molecular genetic PCR methods. The result of cytogenetics:there were 555 abnormal karyotypes of peripheral blood on 5390 cases (10.30%);In 2171 patients who asked for prenatal diagnosis,145 abnormal karyotypes were found (6.68%);We also karyotyped chorionic villous cells of 62 patients with spontaneous abortion and found 28 abnormal karyotypes (45.16%). The PCR results of 23 patients with Down's syndrome were all positive while the results of 155 normal persons were all negative. The method of cytogenetics is very important for diagnosis of abnormal karyotypes;Molecular genetic methods by PCR and FISH are quick,convenient and applicable way.