Search

Abstract: Glycosylation is a widespread modification of plant secondary metabolites, and catalyzed by a superfamily of enzymes called UDP-glycosyltransferases (UGTs). UGTs are often involved in late biosynthetic steps and show broad substrate specificity or regioselectivity. In this study, the acceptor promiscuity of a Rosa hybrid UGT RhGT1 and an evolved microbial UGT OleDPSA toward a small flavonoid library was probed and compared. Interestingly, RhGT1 showed comparable acceptor promiscuity in comparison with OleDPSA, though the acceptor binding pocket of the latter is much more open and large. This clearly indicates that stabilization of the acceptor position by suitable hydrophobic interactions is important for the specificity or regioselectivity determination as well as overall fit of the acceptor into a ‘big enough’ binding pocket. This also poses a challenge for structure-based UGT engineering to alter the glucosylation pattern of flavonoids. [Copyright &y& Elsevier]

Recent studies highlight long non-coding RNAs (lncRNAs) as key regulators of cancer biology that contribute to carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. Previous studies demonstrated that HOTTIP could promote colorectal cancer (CRC) cell proliferation via silencing of p21 expression. However, the potential role of HOTTIP in CRC metastasis has not yet been discussed. Here, we found that HOTTIP level was significantly higher in CRC than in corresponding adjacent normal tissues, and patients with a larger tumor size, advanced pathological stage, or distant metastasis had higher HOTTIP expression. Moreover, silencing HOTTIP expression by siRNA or shRNA could inhibit CRC cell migration and invasion in vitro and in vivo, whereas HOTTIP overexpression promoted cell metastasis, as documented in the SW480 cell lines. Mechanistic analyses indicated that HOTTIP regulates CRC cell metastasis partly through the downregulation of tumor suppressor DKK1 expression. Collectively, our results suggest that tumor expression of lncRNA HOTTIP plays an important role in CRC metastasis. HOTTIP may serve as a candidate biomarker in this disease.

Objectives: The aim of this study was to evaluate the expression of RBM38 protein in gastric cancer patients and to explore its association with clinical pathological characteristics and prognosis., Materials and Methods: A total of 120 pairs of gastric cancer tissues and non-cancerous gastric mucosa from 120 patients who underwent gastrectomy for gastric cancer were included in the current study. RBM38 protein expression levels were detected in all tissue specimens by immunohistochemistry staining. The positive rate of RBM38 was compared between cancer tissue and normal tissue, and its association with the clinical pathological characteristics and prognosis was elucidated., Results: RBM38 protein was predominantly expressed in the cytoplasm of epithelial cells. The percentage of tissues with high RBM38 protein expression level was significantly lower (χ 2 =28.972, P<0.001) in gastric cancer tissues compared with adjacent non-cancerous gastric mucosal tissues. The expression level of RBM38 protein was associated with tumor size (P=0.028), depth of invasion (P<0.001), lymph node metastasis (P<0.001), TNM stage (P<0.001) and Lauren classification of the tumor (P=0.001), whereas it was not associated with gender (P=0.066) and age (P=0.6) of patients. Moreover, we noticed that the low expression level of RBM38 protein was also associated with poor prognosis in gastric cancer patients (log rank =5.325; P=0.021)., Conclusion: Overall, our findings indicated that RBM38 may play a vital role as a tumor suppressor, which may be a potential marker in the diagnosis and prognosis of gastric cancer., Competing Interests: None., (IJCEP Copyright © 2017.)

CD133 is one of the most commonly used markers of pancreatic cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. Although the expression of CD133 has been reported to correlate with poor prognosis of PDAC in most literatures, some controversies still exist. In this study, we aimed to investigate the correlation between CD133 expression and prognosis and clinicopathological features in PDAC. A search in the Medline, EMBASE and Chinese CNKI (China National Knowledge Infrastructure) database (up to 1 March 2015) was performed using the following keywords pancreatic cancer, CD133, AC133, prominin-1 etc. Data from eligible studies were extracted and included into meta-analysis using a random effects model. Outcomes included overall survival and various clinicopathological features. We performed a final analysis of 723 patients from 11 evaluable studies for prognostic value and 687 patients from 12 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD133 for overall survival in PDAC was 0.58 (95% confidence interval (CI): 0.49-0.67) by univariate analysis and 0.73 (95% CI: 0.52-1.03) by multivariate analysis. With respect to clinicopathological features, CD133 overexpression by immunohistochemistry (IHC) method was closely correlated with clinical TNM stage (TNM stage III+IV, OR=0.32, 95% CI: 0.19-0.54), tumor differentiation (poor differentiation, OR=0.56, 95% CI: 0.37-0.83), and lymph node metastasis (N1, 3.15, 95% CI: 1.56-6.36) in patients with PDAC. Our meta-analysis results suggest that CD133 is an efficient prognostic factor in PDAC. Overexpression of CD133 was significantly associated with clinical TNM stage, tumor differentiation and lymph node metastasis.