Abstract. Accumulating evidence reveals that long non-coding RNA (lncRNA) is essential for tumorigenesis and progression, but little is known about its roles and mechanisms in metastatic colorectal cancer (CRC). This study aimed to detect expression level and prognostic role of lncRNA-CTD903 in CRC patients, which was selected based on one microarray data. The effects on cell invasion, migration and proliferation were investigated after silencing or overexpression of CTD903 in CRC cell lines. We also observed the EMT (epithelial-mesenchymal transition) phenomenon and effect on cell adhesion. The associations between CTD903 and EMT markers, such as E-cadherin, N-cadherin, β-catenin, ZEB1, ZO-1, Snail, and Twist, were determined by western blotting. Our results showed lncRNA-CTD903 expression was strongly upregulated in 115 CRC patients, comparing to adjacent normal tissues. CTD903 was proven to be an independent predicted factor of favorable prognosis in CRC patients by using multivariate Cox proportional hazards model. After knockdown of CTD903 in RKO and SW480, both cell invasion and migration increased, and cells exhibited EMT-like appearance, along with reduced adhering ability. Moreover, overexpression of CTD903 in DLD1 and HCT116 reversed these phenotypes. Furthermore, downregulation of CTD903 enhanced Wnt/β-catenin activation and subsequently increased transcription factors (Twist and Snail) expression, along with increased mesenchymal marker Vimentin and decreased epithelial marker ZO-1 level, while overexpressed CTD903 confirmed these associations.In conclusion, this study shows that LncRNA-CTD903 acts as a tumor suppressor in CRC and can inhibit cell invasion and migration through repressing Wnt/β-catenin signaling, which plays important roles in EMT and CRC metastasis.
Angiogenesis is an indispensable mechanism involved in both physiological processes and various pathological conditions, such as inflammation, aberrant wound healing, tumor progression, and metastasis. Among many angiogenic stimulators and inhibitors, vascular endothelial growth factor (VEGF) is regarded as one of the most important members of the signaling protein family involved in blood vessel formation and maturation. The a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) proteins are a family of multifunctional proteinases. Such proteolytic enzymes are associated with various physiological processes, such as collagen maturation, organogenesis, angiogenesis, and reproduction. Importantly, deficiency or overexpression of certain ADAMTS proteinases has been shown to be directly involved in a number of serious diseases, including tumor progression and metastasis. This review explores in-depth the connections between ADAMTS proteinases as positive/negative mediators during angiogenesis and VEGF.
Peste des petits ruminants viruses (PPRVs) re-emerged in China at the end of 2013 and then spread rapidly into 22 provinces through movement of live goats and sheep. In this study, 96 samples of domestic animals and 13 samples of wildlife were analysed for the presence of PPRV infection by ELISA or RT-PCR. Of 96 samples from sheep and goats, 91 were PPRV positive, whereas all of the 13 samples from three wild species, Capra ibex (Capra ibex sibirica), argali (Ovis ammon) and Goitered gazelle (Gazella subgutturosa), were found to be positive. Five wildlife-origin isolates from the above samples were identified as the lineage IV by a multiple alignment of the partial sequences in N gene.
BackgroundA disintegrin and metalloprotease 8 (ADAM8) has been reported to be associated with various malignancies. However, no studies have examined ADAM8 association in colorectal cancer (CRC). The aim of this study was to investigate the expression and function of ADAM8 in CRC.MethodsExpression level of ADAM8 in CRC was evaluated by quantitative RT-PCR, western blot and immunohistochemical staining analysis. The role of ADAM8 in colorectal carcinogenesis was evaluated by in vitro assays. The correlations between ADAM8 status and clinicopathological features including survival were analyzed.ResultsADAM8 was highly expressed in CRC tissues compared with adjacent normal tissues. Knockdown of ADAM8 in two CRC cell lines resulted in reduced cellular growth and proliferation, and increased apoptosis. Immunohistochemistry analysis showed no significant correlations of ADAM8 protein expression with clinicopathologic features. Survival analysis indicated that patients with ADAM8-positive tumors had worse 5-year overall survival (OS, p = 0.037) and 5-year disease free survival (DFS, p = 0.014) compared with those with ADAM8-negative tumors. Multivariate analysis indicated ADAM8 expression was an independent prognostic factor for both OS and DFS (both p< 0.001). Subgroup analysis showed that 5-year OS of colon cancer, T3-T4 stage and N0 stage was worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p< 0.05). The 5-year DFS in colon cancer, T3-T4 stage, N0 stage, TNM stage II, adenocarcinoma, moderate differentiation and male patient subgroups was also worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05).ConclusionsOur results show that ADAM8 is overexpressed in CRC, promotes cell growth and correlates with worse OS and DFS, and thus could serve as a biomarker for individual CRC patient therapy.
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