The global change in protein abundance in colorectal cancer (CRC) and its contribution to tumorigenesis have not been comprehensively analyzed. In this study, we conducted a comprehensive proteomic analysis of paired tumors and adjacent tissues (AT) using high-resolution Fourier-transform mass spectrometry and a novel algorithm of quantitative pathway analysis. 12380 proteins were identified and 740 proteins that presented a 4-fold change were considered a CRC proteomic signature. A significant pattern of changes in protein abundance was uncovered which consisted of an imbalance in protein abundance of inhibitory and activating regulators in key signal pathways, a significant elevation of proteins in chromatin modification, gene expression and DNA replication and damage repair, and a decreased expression of proteins responsible for core extracellular matrix architectures. Specifically, based on the relative abundance, we identified a panel of 11 proteins to distinguish CRC from AT. The protein that showed the greatest degree of overexpression in CRC compared to AT was Dipeptidase 1 (DPEP1). Knockdown of DPEP1 in SW480 and HCT116 cells significantly increased cell apoptosis and attenuated cell proliferation and invasion. Together, our results show one of largest dataset in CRC proteomic research and provide a molecular link from genomic abnormalities to the tumor phenotype.

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Background Cell division cycle associated protein‐3 (CDCA3) has been reported frequently upregulated in various cancers. It has been progressively realized that changed DNA methylations occur in diverse carcinomas. However, the concrete involvement of CDCA3 and DNA methylation in gastric cancer (GC) still needs to be further elucidated. Methods In this study, quantitative reverse‐transcription polymerase chain reaction (PCR) was utilized to determine the relative expressions of CDCA3 in GC and normal tissue samples. The methylation condition of CDCA3 was determined by bisulfite‐sequencing PCR (BSP) and methylation‐specific PCR (MSP). A chromatin immunoprecipitation (ChIP) assay and luciferase activity assay was used for the interaction between transcription factors and promoters and binding site determination, respectively. The effects of knockdown or overexpression of specificity protein 1 (SP1) or CDCA3 on GC cells in vitro were further assessed via wound healing assay, colony formation assay, and matrigel invasion assay. Results In comparison to paired normal tissues, CDCA3 expressions were significantly increased in the GC tissues. The CDCA3 expression was regulated by DNA methylation, with the CpG island hypomethylation responsible for CDCA3 upregulation of GC. ChIP assays verified that the activity of SP1 binding to the CDCA3 promoter was dramatically increased. When the CDCA3 expression was downregulated in MKN45 cells by knockdown SP1, the proliferation ability, healing ability, and invasive ability were significantly suppressed. Conclusion The process by which SP1 bound to the nearest promoter region was expedited in GC cells, by which DNA was hypomethylated and CDCA3 expression was promoted. The effect on cell proliferation and invasion by CDCA3 was under the regulation of SP1 and also affected by hypomethylation of DNA.

Abstract. MicroRNAs (miRNAs) are small non-coding RNAs involved in an array of biological processes, and their dysregulation is associated with tumor development and progression. One such miRNA, miR-219-5p, is abnormally expressed in patients with colorectal cancer (CRC). In the present study, reverse transcription-quantitative polymerase chain reaction was performed to measure miR-219-5p expression in cells from both CRC tumors, and surrounding healthy tissue. MTT and invasion assays were used to determine the role of miR-219-5p in regulating CRC cell proliferation and invasion, respectively. A luciferase assay was then performed to assess the binding of miR-219-5p to the CAPS gene that encodes calcyphosin protein. The present study confirmed that miR-219-5p expression is significantly downregulated in CRC tissue. miR-219-5p knockdown promoted the growth of HCT-8 cells and increased the expression of calcyphosin protein (CAPS). On the other hand, overexpressing miR-219-5p inhibited HCT-8 cell growth and invasion, and downregulated CAPS expression. In addition, CAPS was identified as the functional downstream target of miR-219-5p by directly targeting its 3'-untranslated region. Therefore, miR-219-5p may function as a tumor suppressor by decreasing CAPS expression, and subsequently inhibit tumor proliferation and invasion. These results indicate that novel therapeutic strategies that increase miR-219-5p expression may be developed to treat CRC.

Gastric cancer (GC) is currently the most common malignancy of the gastrointestinal tract, with a high mortality rate that ranks as the second most diagnosed cause of cancer-related death worldwide. 1 According to recent statistics, approximately one million newly diagnosed cases of GC are reported annually, and in 2013, the number of GC-related deaths was nearly 723 000. 2,3 Surgical resection remains the primary treatment for GC patients and can provide the best chance of cure, and chemotherapy and radiotherapy for GC can inhibit tumour cell growth or invasion. 4,5 Despite multiple treatment interventions for GC patients, their 5-year survival rate remains pessimistic due to recurrence and metastasis. 6 Hence, in view of its poor outcomes, GC development and recurrence must be prevented, andThis is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. AbstractObjectives: miR-92b has been reported to play critical roles in several carcinomas; however, our understanding of the mechanisms by which miR-92b stimulates gastric cancer (GC) is incomplete. The aim of this study was to investigate the clinical significance and functional relevance of miR-92b in GC. Materials and methods:Expression of miR-92b in GC and peritumoural tissues was determined using qRT-PCR, in situ hybridization and bioinformatics. CCK-8, colony formation and fluorescence-activated cell sorting assays were utilized to explore the effect of miR-92b on GC cells. A luciferase reporter assay and Western blotting were employed to verify miR-92b targeting of DAB2IP. Furthermore, Western blotting was used to evaluate the levels of DAB2IP and PI3K/Akt signalling pathway-related proteins. Results:In this study, we found that miR-92b was upregulated in GC tissues compared with peritumoural tissues. Overexpression of miR-92b promoted cell proliferation, colony formation, and G 0 /G 1 transition and decreased apoptosis. Our results indicated that miR-92b repressed the expression of DAB2IP and that loss of DAB2IP activated the PI3K/AKT signalling pathway. Overexpression of DAB2IP rescued the effects of miR-92b in GC cells. Finally, our results demonstrated a significant correlation between miR-92b expression and DAB2IP expression in GC tissues. Conclusions:Our results suggest that miR-92b promotes GC cell proliferation by activating the DAB2IP-mediated PI3K/AKT signalling pathway. The miR-92b/DAB2IP/ PI3K/AKT signalling axis may be a potential therapeutic target to prevent GC progression.