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Abstract: MicroRNAs (miRNAs) are directly involved in cancer initiation, progression and metastasis. Alterations of miRNAs expression in cancer tissue may be reflected in circulation. We attempted to investigate the expression and clinical significance of plasma miR-20a, miR-31 and miR-375 in patients with non-small cell lung cancer (NSCLC). The plasma levels of miR-20a, miR-31 and miR-375 in 164 NSCLC patients and 164 healthy controls (discovery cohort) were evaluated and compared among various clinicopathological characteristics. The relationship between miRNA expression and clinical outcome of NSCLC patients was examined in an independent cohort (53 cases and 53 controls). The expression level of miR-375 in tissue was also examined. Plasma miR-375 levels in NSCLC patients were significantly decreased in both patient cohorts (P <0.05). In addition, patients with metastatic NSCLC had lower plasma miR-375 expression than those with non-metastatic NSCLC (P <0.05). Survival analysis showed that patients with low miR-375 expression had worse overall survival rates than those with high miR-375 expression (hazard ratios (HR)=1.537 (1.046–2.258), P =0.029). This association was independently validated in a separate cohort of 53 NSCLC patients (HR=2.406, 95% CI 1.170–4.945, P =0.017). The expression level of miR-375 was also found to be significantly down-regulated in NSCLC tissues compared with paracancerous tissues (P <0.001). These findings indicate that miR-375 has an important role in NSCLC initiation and progression, and may be an independent poor prognostic factor in NSCLC patients. [Copyright &y& Elsevier]

Abstract: The present study was designed to investigate the underlying molecular mechanism for Angiotensin II type 1 receptor blockers (ARBs) mediated cardio-protection against pressure overload-induced cardiac remodeling with a focus on Smad7. ROCK-1, Smad3 and fibronectin expressions were increased in male C57BL/6 mice underwent transverse aortic constriction (TAC) for 2weeks. Treatment with Candesartan (2mg/kg per day) could effectively downregulate Smad3 and fibronectin accompanied by upregulating of Smad7. Further data showed that Candesartan inhibited TGF-β1 signal-induced epithelial-to-mesenchymal transition (EMT) through attenuating matrix metalloproteinases (MMP-9), such effect was abolished by knocking-down Smad7. Moreover, TAC for 2weeks caused increased collagen deposition, thickness of left ventricular anterior and posterior wall at end-diastole (LVAWD and LVPWD) and LVEF% reduction, which were reversed by treatment with Candesartan, but failed after knocking-down Smad7. In addition, LV dP/dtmax and dP/dtmin were increased by TAC for 2weeks, and treatment with Candesartan or Nifedipine effectively depressed the high levels of dP/dtmin induced by TAC. However, only Candesartan-mediated protective role in improving cardiac function was suppressed by tail-vein injection of Smad7 siRNA. This study uncovered a novel role for ARBs in preventing pressure overload-induced cardiac remodeling via Smad7 upregulation, which suppressed MMP-9 expression and TGF-β1 signal-mediated EMT progress. [Copyright &y& Elsevier]

• Molecular characteristics and expressions of POU family genes in C. gigas were examined. • CgPOU3F4-like was a transcriptional factor in activating CgB-aat1 gene promoter. • CgPOU3F4-like positively regulated CgB-aat1 gene expression. • CgPOU3F4-like knockdown led to decreases of CgB-aat1 and CgCbs expressions. Previous study has found that b (0, +) -type amino acid transporter 1 (CgB-aat1) plays an essential role on mantle pigmentation in the Pacific oyster Crassostrea gigas. However, the molecular regulation of CgB-aat1 gene expression remains unclear. Herein, three POU domain family members, CgPOU2F1 , CgPOU3F4-like and CgPOU4F3-X1 were characterized and they all had POUs and HOX domains, respectively, which were important in transcriptional regulation. CgPOU3F4-like gene expression was the highest in mantle edge. Subsequently, the dual-luciferase reporter result showed that the core regulatory region of CgB-aat1 gene was from −632 to −350 bp of promoter. In transient co-transfection assays, the strongest activity was activated only by CgPOU3F4-like, suggesting CgPOU3F4-like was a valid transcriptional activator of CgB-aat1 gene promoter. And the structural integrity of CgPOU3F4-like was essential for its activation function. In addition, site directed mutagenesis assay was applied to detect three key binding sites between CgPOU3F4-like and core region of CgB-aat1 gene promoter, and this interaction was verified by ChIP test. Furthermore, CgPOU3F4-like knockdown by RNA interference led to obvious decreases in CgB-aat1 and cystathionine beta-synthase (CgCbs) expressions at both mRNA and protein levels. Collectively, these results indicate that CgPOU3F4-like positively regulate Cg B-aat1 gene expression and it may be a critical upstream transcriptional regulation factor in pheomelanin synthesis in C. gigas. [ABSTRACT FROM AUTHOR]

• Carotenoid metabolism of Crassostrea gigas was studies for the first time with a beta-carotene feeding method. • The function of two apolipoprotein genes in carotenoid storage was validated by RNAi in the oyster. • A negative feedback regulation mechanism was proposed to regulate carotenoid metabolism in the oyster. Carotenoids are essential micronutrients for animals, and they can only be obtained from the diet for mollusk as well as other animals. In the body, carotenoids undergo processes including absorption, transport, deposition, and metabolic conversion; however, knowledge of the involved genes is still limited. To elucidate the molecular mechanisms of carotenoid processing and identify the related genes in Pacific oyster (Crassostrea gigas), we performed a comparative transcriptome analysis using digestive gland tissues of oysters on a beta-carotene supplemented diet or a normal diet. A total of 718 differentially expressed genes were obtained, including 505 upregulated and 213 downregulated genes in the beta-carotene supplemented group. Function Annotation and enrichment analyses revealed enrichment in genes possibly involved in carotenoid transport and storage (e.g., LOC105342035), carotenoid cleavage (e.g., LOC105341121), retinoid homeostasis (e.g., LOC105339597) and PPAR signaling pathway (e.g., LOC105323212). Notably, down-regulation of mRNA expressions of two apolipoprotein genes (LOC105342035 and LOC105342186) by RNA interference significantly decreased the carotenoid level in the digestive gland, supporting their role in carotenoid transport and storage. Based on these differentially expressed genes, we propose that there may be a negative feedback mechanism regulated by nuclear receptor transcription factors controlling carotenoid oxygenases. Our findings provide useful hints for elucidating the molecular basis of carotenoid metabolism and functions of carotenoid-related genes in the oyster. [ABSTRACT FROM AUTHOR]

Abstract: Dicer, Argonaute and RNA-dependent RNA polymerase form the core components to trigger RNA silencing. Although tomato (Solanum lycopersicum) is a dicotyledon model plant, no systematic analysis and expression profiling of these genes in tomato has been undertaken previously. In this study, seven Dicer-like (SlDCLs), 15 Argonaute (SlAGOs) and six RNA-dependent RNA polymerase (SlRDRs) genes were identified in tomato. These genes were categorized into four subgroups based on phylogenetic analyses. Comprehensive analyses of gene structure, genomic localization and similarity among these genes were performed. Their expression patterns were investigated by means of expression models in different tissues and organs using online data and semi-quantitative RT-PCR. Many of the candidate genes were up-regulated in response to Tomato yellow leaf curl virus infection and abiotic stresses. The expression models of tandem gene duplications among SlDCL2s indicated the DCL2 family plays an important role in the evolution of tomato. [Copyright &y& Elsevier]