CircRNA_MYLK promotes malignant progression of ovarian cancer through regulating microRNA-652.

OBJECTIVE: The purpose of this study was to investigate circRNA_MYLK level in ovarian cancer (OC), and to further investigate whether it could promote the malignant progression of OC via regulating microRNA-652. PATIENTS AND METHODS: quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine circRNA_MYLK level in 46 tumor tissue specimens and paracancerous normal ones collected from OC patients, and the interplay between circRNA_MYLK expression and clinical indicators of OC and patient prognosis was analyzed. Meanwhile, qPCR was also used to further verify circRNA_MYLK level in OC cell lines. In addition, circRNA_MYLK knockdown model was constructed using lentivirus in OC cell lines including A2780 and CAOV3, and the impacts of circRNA_MYLK on the biological functions of OC cells was evaluated using Cell Counting Kit-8 (CCK-8) and cloning experiments. Finally, Luciferase reporting assay and recovery experiment were performed to investigate the regulatory interplay between circRNA_MYLK and microRNA-652. RESULTS: qPCR results indicated that circRNA_MYLK level in OC patients was remarkably higher than that in adjacent ones, and the difference was statistically significant. Compared with patients with low expression of circRNA_MYLK, patients with high expression of circRNA_MYLK had a higher pathological staging and a lower overall survival rate. Compared with the control group (sh-NC), the OC cell proliferation ability was remarkably attenuated in the circRNA_MYLK knockdown group (sh-circRNA). In addition, qPCR verification revealed that the expression levels of microRNA-652 and circRNA_MYLK were negatively correlated in OC tissues. At the same time, bioinformatics analysis and Luciferase reporter gene assay results confirmed that circRNA_MYLK can be targeted by microRNA-652. Finally, it was found that simultaneous knockdown of circRNA_MYKK and microRNA-652 could reverse the enhanced OC cell proliferative capacity induced by downregulation of circRNA_MYLK alone. CONCLUSIONS: CircRNA_MYLK may promote the malignant progression of OC via regulating microRNA-652, and its expression was remarkably associated with pathological staging and poor prognosis in patients with OC.

miR-520h is crucial for DAPK2 regulation and breast cancer progression.

This corrects the article DOI: 10.1038/onc.2015.168.

Shorter hemodialysis duration is a risk factor for the recurrence of urothelial carcinoma of the bladder in patients on maintenance hemodialysis.

PURPOSE: To investigate the association of hemodialysis duration with the recurrence of urothelial carcinoma (UC) of the bladder and overall survival in patients undergoing maintenance hemodialysis (MHD). PATIENTS AND METHODS: 52 bladder cancer patients who underwent MHD at the Xiangya Hospital of The Central South University between 2001 and 2011 were enrolled in the study. The patients were divided into three groups according to hemodialysis duration, and patient mortality and tumor recurrence rates were analyzed. The association of hemodialysis duration with occurrence and recurrence of UC of the bladder was analyzed by Cox regression analysis. Survival was evaluated by the Kaplan-Meier method. RESULTS: Out of 6266 chronic hemodialysis patients, 52 patients had UC of the bladder after the initiation of hemodialysis for 6 months. The mean age at hemodialysis onset was 55 years (IQR 36, 71). The major complaints were painless gross hematuria and urethral bloody discharge. Tumors were generally large and multifocal. The standardized incidence ratio of UC of the bladder was 43.9 compared with general population, and it was higher in women (76.7) and in the age group 61-65 years (186.6). The mean hemodialysis duration before the diagnosis of bladder cancer was 32 months. 30 (57.7 %) patients received hemodialysis no more than 3 years, 10 (19.2 %) patients received hemodialysis between 3 and 6 years, and 12 (23.1 %) patients received hemodialysis for more than 6 years. CONCLUSION: Preoperative shorter hemodialysis duration is a risk factor for the occurrence and recurrence of UC of the bladder in patients undergoing MHD.

miR-520h is crucial for DAPK2 regulation and breast cancer progression.

MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their interaction with 3'untranslated region of specific target mRNAs. Although the dysregulation of miRNAs has been identified in human cancer, only a few of these miRNAs have been functionally documented in breast cancer. Thus, defining the important miRNA and functional target involved in chemoresistance is an urgent need for human breast cancer treatment. In this study, we, for the first time, identified a key role of miRNA 520h (miR-520h) in drug resistance. Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. Furthermore, we observed that higher level of miR-520h is associated with poor prognosis and lymph node metastasis in human breast cancer patients. These results show that miR-520h is not only an independent prognostic factor, but is also a potential functional target for future applications in cancer therapeutics.

Identification and molecular characterisation of HMW glutenin subunit 1By16* in wild emmer.

In this study, a novel y-type high molecular weight glutenin subunit (HMW-GS) in wild emmer wheat Triticum turgidum L. var. dicoccoides (Körn.) accession KU1952 was identified by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), capillary electrophoresis (CE) and matrix-assisted laser desorption ionisation/time-of-flight/mass spectrometry (MALDI-TOF-MS). Its electrophoretic mobility and molecular weight were similar to those of 1By16 and was designated as 1By16*. The complete coding sequence of the 1By16* gene isolated by allelic-specific polymerase chain reaction (AS-PCR) consists of 2,157 bp, encoding 729 amino acid residues. The real presence and authenticity of the 1By16* gene in KU1952 were further confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), heterologous expression and Western blotting. The molecular structure as well as phylogenetic analysis revealed that 1By16* had 21 single-nucleotide polymorphism (SNP) variations and possessed greater similarity with superior quality subunits 1By15 and 1By16 of common wheat. Secondary structure prediction displayed higher α-helix and ß-strand contents in the 1By16* subunit, which could form a superior gluten structure and, consequently, might have positive effects on dough quality. Our results suggest that 1By16* is expected to be a new potential gene for wheat quality improvement.