LncRNA UBE2R2-AS1, as prognostic marker, promotes cell proliferation and EMT in prostate cancer.

BACKGROUND: Long noncoding RNA ubiquitin-conjugating enzyme E2 R2 antisense RNA 1 (UBE2R2-AS1) has been recently reported to participate in the progression of tumors, including glioma and liver cancer. However, the roles of UBE2R2-AS1 in prostate cancer (PC) remained poorly understood. METHODS: The expression of UBE2R2-AS1 was determined in tumor tissues and paired adjacent tissues from PC patients using quantitative reverse transcription PCR analysis. Correlation between UBE2R2-AS1 expression and clinicopathological parameters and overall survival were investigated by Chi-square test and Kaplan-Meier method analysis. The in vitro experiments, including CCK-8 assay, colony formation, flow cytometry and transwell assay were performed to investigate the functional role of UBE2R2-AS1 knockdown or overexpression on PC cell lines (PC-3 and DU145). Related protein expression levels were measured by western blot analysis. RESULTS: Our data showed that UBE2R2-AS1 expression was significantly upregulated in PC tissues compared with that in adjacent tissues. The high levels of UBE2R2-AS1 were associated with high Gleason score, advanced clinical T stage, lymph node metastasis and poor prognosis. Knockdown of UBE2R2-AS1 suppressed cell proliferation, migration and invasion, induced cell cycle G0/G1 arrest and apoptosis in PC cells, along with decreased expression of PCNA, CDK4, Cyclin D1, Bcl-2, N-cadherin and Vimentin, and increased E-cadherin expression. Overexpression of UBE12R2-AS1 obtained the opposite results in PC cells. CONCLUSIONS: Our findings suggest that UBE2R2-AS1 might be a potential diagnostic and/or therapeutic target in PC.

Antimicrobial mexicanolide limonoids from the seeds of Khaya senegalensis.

Three new mexicanolide limonoids were obtained from the 90% ethanol extract of the seeds of Khaya senegalensis. Their structures were elucidated as senegalenines A-C (1-3) by analysing their 1D/2D NMR and MS spectroscopic analysis. In addition, the isolated limonoids were tested in vitro for antimicrobial potentials against 5 pathogenic microorganisms. Consequently, compounds 1-3 exhibited antimicrobial activity against the tested Gram negative bacteria at the minimum inhibitory concentration values less than 40 µg/ml.

Upregulation of circular RNA circ_0000502 predicts unfavorable prognosis in osteosarcoma and facilitates cell progression via sponging miR-1238.

Growing evidence suggests that circular RNAs (circRNAs) play a significant role in regulating cancer initiation and metastasis. Osteosarcoma (OS) is a sophisticated disease with various genes activated or silenced. In this study, we defined a novel cancer-related circRNA, circ_0000502 in OS progression. qRT-PCR was conducted to detect its expression level in OS tissue samples and cell lines. In addition, the clinical significance of circ_0000502 was investigated. Afterwards, gain-of-function and loss-of-function in vitro assays were performed to detect the cell growth, apoptosis, migration, and invasion altered by circ_0000502 by CCK-8, clone-forming, flow cytometry, and transwell experiments. Xenograft study was performed to validate the in vitro data. The luciferase reporter assay was used to explore the mechanism of circ_0000502. Circ_0000502 was identified upregulated in both OS tissue specimens and cells. In addition, its expression predicts clinical severity and unfavorable prognosis in the 63 recruited patients with OS. Circ_0000502 facilitated cell proliferation, migration, and invasion in OS cells and inhibited cell apoptosis. The animal study further confirmed the in vitro results. For mechanism exploration, circ_0000502 could directly sponge microRNA (miR)-1238, and the oncogenic functions of circ_0000502 is partially dependent on its regulation of miR-1238 proved by rescue assays. In summary, this study might help to develop rational predictive and therapeutic target for patients with OS.

Upregulated long noncoding RNA LINC01296 indicates a dismal prognosis for pancreatic ductal adenocarcinoma and promotes cell metastatic properties by affecting EMT.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to chemotherapy and radiotherapy and whose incidence has increased worldwide. Long noncoding RNAs have been demonstrated to play important roles in cancer initiation and progression. Long intergenic non-coding RNA 01296 (LINC01296) has been reported to be upregulated in several malignancies, but the clinical relevance and biological role of LINC01296 in PDAC are still unclear. METHODS: RT-qPCR was performed to evaluate the expression of LINC01296 in 85 pared PDAC tissue samples and a panel of PDAC cell lines. The clinical value and prognostic role of LINC01296 in patients with PDAC were further explored. Furthermore, we explored the functional roles of LINC01296 depletion in PANC-1 and SW1990 cells, including cell proliferation, apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT). RESULTS: LINC01296 was enhanced in PDAC tissues and cell lines, and this overexpression was correlated with advanced tumor stages and positive lymph node metastasis in patients with PDAC. In addition, upregulation of LINC01296 was an independent prognostic predictor for patients with PDAC after surgery. Moreover, silencing of LINC01296 followed by treatment with small interfering RNAs suppressed cell proliferation and promoted cell apoptosis by affecting the Bcl-2/caspase-3 pathway. Importantly, LINC01296 attenuation impaired the migratory and invasive potential partly by reversing EMT. CONCLUSIONS: Overall, our work may help to develop a novel prognostic biomarker and therapeutic target for PDAC.

Cytotoxic and antibacterial aspidofractinine alkaloids from Kopsia hainanensis.

The ethanol extract of the twigs and leaves of Kopsia hainanensis afforded six new aspidofractinine alkaloids, kopsiahainanins A-F (1-6), among which alkaloids 1 and 2 possessed a lactone bridge with novel regiochemistry. The structures of the isolated compounds were established based on 1D and 2D (1H1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested in vitro for cytotoxic activity against seven tumor cell lines and antibacterial activities against two Gram-positive bacteria and five Gram-negative bacteria. As a result, alkaloids 1 and 2 exhibited cytotoxic activities (IC50 values <20 µM) against all tested tumor cell lines and significant antibacterial properties (MIC values from 0.12 to 0.26 mM).

Enhanced expression of lncRNA TP73-AS1 predicts adverse phenotypes for cholangiocarcinoma and exerts oncogenic properties in vitro and in vivo.

Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with increasing incidence worldwide. Various evidence documents that abnormally expressed long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression. TP73-AS1 is a novel cancer-related lncRNA that contributes to the development of several malignancies. However, its clinical value and potential effects on CCA remains unknown. RT-qPCR was used to measure the expression levels of TP73-AS1 in CCA tissues and paired non-tumor tissues and the association between TP73-AS1 expression and clinicopathological characteristics was analyzed. In addition, the functional roles of TP73-AS1 in CCA were detected both in vitro and in vivo. The results illustrated that TP73-AS1 transcription is enhanced in both CCA tissue samples and cell lines, and this upregulation is closely associated with larger tumor size (p=0.008) and advanced TNM stage (p=0.026) in patients with CCA. For the part of functional assays, silencing of TP73-AS1 could attenuate CCA cell growth both in vitro and in vivo. Additionally, silencing of TP73-AS1 facilitates apoptosis via activating caspase-3 and caspase-9. Importantly, TP73-AS1 expression did not affect HIBEC cell growth and apoptosis. Moreover, TP73-AS1 could also facilitate migration and invasion potential of CCA cells. Collectively, these findings may help to develop a potential therapeutic target for the patients with CCA.

A novel prognostic biomarker for pancreatic ductal adenocarcinoma: hsa_circ_0001649.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with increasing incidence worldwide. Accumulating evidence indicated that circular RNAs (circRNAs) behave as a novel class of transcription products during multiple cancer processes. Specifically, hsa_circ_0001649 has been reported to be down-regulated in several cancers. However, its clinical significance and functional roles in PDAC is still unknown. RT-qPCR was carried out to measure the expression of hsa_circ_0001649 in PDAC tissue samples and cell lines. Additionally, the correlation between hsa_circ_0001649 expression and clinicopathological features was analyzed. The prognostic role of hsa_circ_0001649 was explored by Cox regression analysis. The potential effects of hsa_circ_0001649 in PDAC cells were evaluated in vitro including cell proliferation, colony-forming ability and apoptosis. As a result, hsa_circ_0001649 was abnormally decreased in PDAC tissues and cells, and this down-regulation was correlated with tumor stage and differentiation grade in PDAC patients. Hsa_circ_0001649 could serve as an independent prognostic factor for PDAC patients after surgery. What's more, increased hsa_circ_0001649 caused tumor suppressive effects via reducing cell proliferation, colony-forming ability and promoting cell apoptosis in PANC1 and BxPC3 cells. Collectively, the results illustrated that hsa_circ_0001649 may play a tumor suppressor role in PDAC and offer a potential therapeutic target for treating this fatal disease.

An increased expression of long non-coding RNA PANDAR promotes cell proliferation and inhibits cell apoptosis in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies worldwide. Emerging evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) act as imperative roles in tumorigenesis and progression. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) is a novel lncRNA that contributes to the development of various cancers. However, its clinical significance and potential effects on PDAC remains unknown. In the present study, qRT-PCR was performed to explore the expression levels of PANDAR in PDAC tissues and corresponding non-tumor tissues, the correlation between PANDAR expression and clinicopathological characteristics was also analyzed. The functional roles of lncRNA PANDAR in PDAC cells were evaluated both in vitro and in vivo. The results indicated that PANDAR was aberrantly overexpressed in PDAC tissues and cell lines, and this overexpression was closely associated with tumor stage and vascular invasion in PDAC patients. Besides, silencing of PANDAR exerted tumor suppressive effect via reducing cell proliferation, colony-forming ability, inducing cell cycle G0/G1 arrest and apoptosis in PANC1 and Capan-2 cells. Further in vivo study confirmed the oncogenesis role of PANDAR in PDAC cells. Overall, our findings may help to develop a potential therapeutic target for the patients with PDAC.

Impact of Chemotherapy Delay on Overall Survival for AML with IDH1/2 Mutations: A Study in Adult Chinese Patients.

The effect of time from diagnosis to treatment (TDT) on overall survival of patients with acute myeloid leukemia (AML) remains obscure. Furthermore, whether chemotherapy delay impacts overall survival (OS) of patients with a special molecular subtype has not been investigated. Here, we enrolled 364 cases of AML to assess the effect of TDT on OS by fractional polynomial regression in the context of clinical parameters and genes of FLT3ITD, NPM1, CEBPA, DNMT3a, and IDH1/2 mutations. Results of the current study show IDH1/2 mutations are associated with older age, M0 morphology, an intermediate cytogenetic risk group, and NPM1 mutations. TDT associates with OS for AML patients in a nonlinear pattern with a J shape. Moreover, adverse effect of delayed treatment on OS was observed in patients with IDH1/2 mutations, but not in those with IDH1/2 wildtype. Therefore, initiating chemotherapy as soon as possible after diagnosis might be a potential strategy to improve OS in AML patients with IDH1/2 mutations.

An improved MLVF method and its comparison with traditional MLVF, spa typing, MLST/SCCmec and PFGE for the typing of methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has become an important nosocomial pathogen, causing considerable morbidity and mortality. During the last 20 years, a variety of genotyping methods have been introduced for screening the prevalence of MRSA. In this study, we developed and evaluated an improved approach capillary gel electrophoresis based multilocus variable-number tandem-repeat fingerprinting (CGE/MLVF) for rapid MRSA typing. A total of 42 well-characterized strains and 116 non-repetitive clinical MRSA isolates collected from six hospitals in northeast China between 2009 and 2010 were tested. The results obtained by CGE/MLVF against clinical isolates were compared with traditional MLVF, spa typing, Multilocus sequence typing/ staphylococcal cassette chromosome mec (MLST/SCCmec) and pulse field gel electrophoresis (PFGE). The discriminatory power estimated by Simpson's index of diversity was 0.855 (28 types), 0.855 (28 patterns), 0.623 (11 types), 0.517 (8 types) and 0.854 (28 patterns) for CGE/MLVF, traditional MLVF, spa typing, MLST/SCCmec and PFGE, respectively. All methods tested showed a satisfied concordance in clonal complex level calculated by adjusted Rand's coefficient. CGE/MLVF showed better reproducibility and accuracy than traditional MLVF and PFGE methods. In addition, the CGE/MLVF has potential to produce portable results. In conclusion, CGE/MLVF is a rapid and easy to use MRSA typing method with lower cost, good reproducibility and high discriminatory power for monitoring the outbreak and clonal spread of MRSA isolates.