Several pathologic characteristics of the primary tumor are correlated with the outcome of esophagectomy for squamous carcinoma of the thoracic esophagus. Patients with fewer than 2 metastatic nodes after curative esophagectomy have a better prognosis than those with multiple involved nodes (>2). To stratify patients appropriately for prognosis, it is necessary to refine the current 6th edition TNM staging system.

BackgroundMany long non coding RNAs have been identified as key modulators in cancer development. A lncRNA, DBCCR1-003, derived from the locus of tumor suppressor gene DBCCR1 (deleted in bladder cancer chromosome region 1), has unknown function. In the present study, we explored function and molecular mechanism of DBCCR1-003 in bladder cancer (BC) development.MethodsWe evaluated the expression levels of DBCCR1-003 in tissues and cells with western blot and quantitative real-time polymerase chain reaction. Multiple approaches including chromatin immunoprecipitation assay and RNA immunoprecipitation were used to confirm the direct binding of DBCCR1-003 to DNMT1. The recombinant vector overexpressing DBCCR1-003 was constructed. Cell proliferation assay, colony formation assay and flow cytometric analysis were employed to measure the role of DBCCR1-003 in regulation of cell proliferation, cycle and apoptosis.ResultsFirstly we detected the expression of DBCCR1-003, DBCCR1, DNMT1 (DNA methyltransferase 1) and DNA methylation in the promoter of DBCCR1. We found low expression of DBCCR1-003, same as DBCCR1, while high expression of DNMT1 and hypermethylation of DBCCR1 gene promoter in BC tissues and T24 cells line. Further studies revealed that treatment of DNMT inhibitor, 5-aza-2-deoxycytidine(DAC), or overexpression of DBCCR1-003 led to increased DBCCR1 expression by reversion of promoter hypermethylation and DNMT1 binding to DBCCR1 promoter in T24 cells. Importantly, RNA immunoprecipitation (RIP) showed that DBCCR1-003 physically associates with DNMT1. The binding of them was increased with the inhibition of DBCCR1 promoter methylation, indicating that DBCCR1-003 may bind to DNMT1 and prevent DNMT1-mediated the methylation of DBCCR1. Furthermore, overexpression of DBCCR1-003 resulted in significant inhibition of T24 cells growth through the inducing G0/G1 arrest and apoptosis.ConclusionsTaken together, these findings demonstrated that a novel tumor suppressor DBCCR1-003 regulates the expression of DBCCR1 via binding to DNMT1 and preventing DNMT1-mediated the methylation of DBCCR1 in BC. LncRNA DBCCR1-003 may serve as a novel biomarker and therapeutic target for BC in future cancer clinic.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-016-0356-8) contains supplementary material, which is available to authorized users.

miR-186 has been reported to be implicated in tumorigenesis and chemoresistance in a few cancer types. However, its role in regulating chemoresistance has not been investigated in non-small cell lung cancer (NSCLC). To examine the effects of miR-186 on chemosensitivity in NSCLC, an miR-186 mimic and inhibitor were transfected, followed by CellTiter-Glo® assay in NSCLC cell lines. Western blot and luciferase assay were performed to investigate the direct targeting of miR-186. A xenograft mouse model was used to examine the in vivo chemosensitizing function of miR-186. We found that overexpression of miR-186 sensitized A549 and H1299 cells to paclitaxel, whereas inhibition of miR-186 conferred resistance in these cells. MAPT was the direct target of miR-186 which was required for the regulatory role of miR-186 in chemoresistance. This chemosensitizing function was partially due to the induction of the p53 mediated apoptotic pathway. The miR-186 mimic enhanced the tumor growth inhibitory effects of paclitaxel in A549 xenografts. In addition, miR-186 was found to be down-regulated in NSCLC patients who were chemoresistant and this down-regulation was associated with poor survival. Taken together, our study demonstrated that miR-186 regulates the chemoresistance of NSCLC cells by modulating the MAPT expression level both in vitro and in vivo. miR-186 may represent a new therapeutic target for the improvement of the clinical outcome in NSCLC.

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