Background/purposeCell adhesion molecule 1 (CADM1) functions as a tumor suppressor and has been identified to be frequently inactivated in breast cancer, and closely associated with patients’ poor prognosis and advanced TNM stage. However, the mechanisms underlying CADM1 in breast cancer progression remains incompletely clear. miR-155, a predicted modulator of CADM1 was reported to be overexpressed in breast cancer, and its high expression level was closely related to the malignant progression of breast cancer. The present study aimed to explore whether miR-155-3p could modulate CADM1 expression and then involved in the progression of breast cancer.MethodsThe expression patterns of miR-155-3p in breast cancer tissues and cell lines were determined by RT-PCR technology. The relationship between CADM1 and miR-155-3p were determined by the luciferase gene reporter and Western Blot (WB) assays. Cell proliferation, apoptosis rates and tumorigenesis were determined by CCK-8, flow cytometry and in vivo xenotransplanation experiments, respectively.ResultsmiR-155-3p was up-regulated in breast cancer tissues and cells when compared to the adjacent normal tissues and normal breast MCF 10A cells. The mRNA and protein levels of CADM1 showed opposite expression patterns to that of miR-155-3p expression detected, and miR-155-3p could negatively regulate CADM1 expression in breast cancer MCF-7 cells. Moreover, gain-of function assay showed that overexpression of miR-155-3p promoted cell proliferation, tumorigenesis and repressed cell apoptosis, but these effects were all significantly impaired when the cells were simultaneously transfected with OE-CADM1, the overexpressing vector of CADM1.ConclusionThis study revealed that miR-155-3p could accelerate the progression of breast cancer via down-regulation of CADM1 expression.

Ovarian cancer is a lethal gynecologic malignancy and always has a poor prognosis. Despite new treatments modalities, the long term outcomes had not been significantly improved in the past 30 years. Although has been reported to be a prognostic marker in ovarian cancer, it's exact role in ovarian cancer remain unclear. In this study, we inserted the response element of miR-200a in ovarian cancer cell line via lentivirus-mediated transgene in vitro, and qRT-PCR (real time quantitative reverse transcription PCR) assay confirmed that miR-200a was up regulated compared with control. Then colony-formation assay, cell cycle analysis, CCK8 assays in vitro and xenograft experiments in vivo were performed and verified that miR-200a promoted proliferation, while blocked the formation of tumor spheroids and reduced the ratio of SP (side population) cells in ovarian cancer. Finally, we validated that miR-200a significantly enhanced the chemosensitivity of paclitaxel but not cisplatin in both adherent culture and sphere culture. Taken together, we demonstrated that upregulation miR-200a promoted proliferation and inhibited cancer stem cells (CSCs) phenotype in OVCAR-3 ovarian cancer cell line, combined with cell cycle-targeting drug paclitaxel could effectively eliminate the "side effects" of proliferation, and showed evidences that this strategy may be promising for ovarian cancer treatment. Key words: microRNA, ovarian cancer, proliferation, cancer stem cells, chemosensitivityOvarian cancer is still the most lethal gynaecologic malignancy according to 2013 statistics [1]. Although the current standard treatment, systemic by administration of platinum and paclitaxel after debulking surgery was efficient in almost 70% of ovarian cancer cases, most of these patients ultimately develop chemoresistance and recurrence [2].Recently, accumulated evidence showed that the miR-200a expression level was closely associated with progression free survival (PFS), overall survival (OS) and chemo-sensitivity in ovarian cancer, thus miR-200a was suitable as a prognostic marker for ovarian cancer outcome [3,4]. Previously, we demonstrated that the profile of miRNAs was different between CD133+ and CD133 -ovarian cancer cells, miR-200a was down-regulated in CD133 + ovarian cancer stem cells (CSCs) [5], and upregulation miR-200a could reduce ZEB2-mediated migration and invasion of CD133 + ovarian CSCs [6]. However, miR-200a regulation of proliferation, CSCs phenotype and chemosensitivity in ovarian cancer remain unclear. Therefore, an in-depth understanding of the roles and mechanisms of miR-200a in ovarian cancer is needed.Herein, we first established that miR-200a was stably overexpressed in OVCAR-3 ovarian cancer cell line and then validated that over-expression of miR-200a increased tumor proliferation and tumor volume. Additionally, we found that the over-expression of miR-200a weakened the CSCs phenotype by blocking the formation of tumor spheroids and reducing the ratio of side population (SP) cells. Importantly, we demonstrated miR-200...

The dysregulation of exosomal microRNAs (miRNAs) plays a crucial role in the development and progression of cancer. This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer (GC) and the underlying mechanisms. The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics. Next, the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues, and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments. Then, the effect of miR-4256 on its downstream target genes HDAC5/p16 INK4a was studied in GC cells, and the underlying mechanisms were evaluated using dual luciferase reporter assay and Chromatin Immunoprecipitation (ChIP). Additionally, the role of the miR-4256/HDAC5/p16 INK4a axis in GC was studied using in vitro and in vivo experiments. Finally, the upstream regulators SMAD2/p300 that regulate miR-4256 expression and their role in GC were explored using in vitro experiments. miR-4256 was the most significantly upregulated miRNA and was overexpressed in GC cell lines and GC tissues; in vitro and in vivo results showed that miR-4256 promoted GC growth and progression. Mechanistically, miR-4256 enhanced HDAC5 expression by targeting the promoter of the HDAC5 gene in GC cells, and then restrained the expression of p16 INK4a through the epigenetic modulation of HDAC5 at the p16 INK4a promoter. Furthermore, miR-4256 overexpression was positively regulated by the SMAD2/p300 complex in GC cells. Our data indicate that miR-4256 functions as an oncogene in GC via the SMAD2/miR-4256/HDAC5/p16 INK4a axis, which participates in GC progression and provides novel therapeutic and prognostic biomarkers for GC.