Pseudogenization of Mc1r gene associated with transcriptional changes related to melanogensis explains leucistic phenotypes in Oreonectes cavefish (Cypriniformes, Nemacheilidae)

Organisms that have colonized underground caves encounter vastly different selective pressures than their relatives in above‐ground habitats. While disruption of certain pigmentation genes has been documented in various cave‐dwelling taxa, little is known about wider impacts across pigmentation and other gene pathways. We here study the timeframe and transcriptional landscape of a leucistic and blind cypriniform fish (Oreonectes daqikongensis, Nemacheilidae) that inhabits karst caves in Guizhou, China. Based on data from the mitochondrial ND4, ND5, and Cytb genes, we show that the divergence between O. daqikongensis and its most closely related pigmented species occurred ca. 6.82 million years ago (95% HPD, 5.12–9.01), providing ample time for widespread phenotypic change. Indeed, we found that the DNA sequence of Mc1r (melanocortin‐1 receptor), a key gene regulating the biosynthesis of melanin in most vertebrates, is pseudogenized in O. daqikongensis, caused by a 29 bp deletion in the protein‐coding region. Furthermore, 99,305 unigenes were annotated based on the transcriptome of skin tissue of Oreonectes fish. Among the differentially expressed unigenes, 7,326 (7.4% of the total unigenes) had decreased expression and 2,530 (2.5% of the total unigenes) had increased expression in O. daqikongensis skin. As predicted, the expression of Mc1r and 18 additional genes associated with melanin biosynthesis was significantly downregulated in the skin tissue of O. daqikongensis, but not in its congener. Our results, integrating with other studies on cavefishes, suggest that loss of pigmentation was caused by coding region loss‐of‐function mutations along with widespread transcriptional changes, resulting from extended evolutionary time as a cave‐dwelling form

Complete mitochondrial genome of Triplophysa nasobarbatula

The complete mitochondrial DNA genome of Triplophysa nasobarbatula was sequenced and characterized. Triplophysa nasobarbatula revealed that the complete length of its mitochondrial genome was 16,316 bp, composed of A (29.71%), C (24.79%), G (17.22%), T (28.29%), A + T (57.99%), and C + G (42.01%). Its genetic constitution and arrangement were consistent with the taxon of the Teleost, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 2 main non-coding regions, D-loop region and OL region. All genes were encoded by the H-strand, except for 1 protein-coding gene (ND6) and 8 tRNA genes (tRNA-Gln, tRNA-Ala, tRNA-Cys, tRNA-Asn, tRNA-Tyr, tRNA-Ser, tRNA-Glu and tRNA-Pro) are encoded by the L-strand. Our mitochondrial genome data may provide information for taxonomic resolution, taxonomic resolution, and other studies about this genus of Triplophysa

A new blind species of the cave genus Oreonectes from Guizhou, China (Nemacheilinae)

This study aimed to describe a new specimen of cavefish collected from a karst cave in the Daqikong area of Libo County, Guizhou. Twenty-six cavefish specimens were collected and identified as a new species of Balitoridae: Nemacheilinae, and named Oreonectes daqikongensis sp. n. A genetic analysis was performed and showed that its genetic distances from Oreonectes shuilongensis and Oreonectes platycephalus are higher than intraspecific distances. Discovery of this species will be helpful to understand the distribution of Oreonectes

Maternal Daidzein Supplementation during Lactation Promotes Growth Performance, Immunity, and Intestinal Health in Neonatal Rabbits

The main purpose of the present research was to evaluate the effect of varying levels of DA inclusion in maternal diet, in the form of powder, on the born-weaning growth performance (days 1–30) and intestinal health of neonatal rabbits. A total of 152 delivered maternal does (3.94 ± 0.05 kg) were allocated into four groups, with thirty-eight replicates of one doe each, and fed with a control diet (CON) supplemented with different levels of powdered DA (85 mg/kg (DA85), 170 mg/kg (DA170), and 340 mg/kg (DA340)) during lactation. The results show that dietary DA increased individual body weight at days 21 and 30 (p = 0.03 and p p p = 0.05) and glutathione peroxidase (GSH-Px) (p = 0.01) concentrations of maternal rabbits were increased in all maternal DA-supplemented groups and showed a linear and quadratic effect (p p p p p = 0.01) in neonatal rabbits were increased in all dietary DA groups, and both showed a linear and quadratic effect (p p = 0.03) and catalase (CAT) (p = 0.04) concentrations were affected by DA supplements, but linear and quadratic effects were only observed in the catalase (CAT) of neonatal rabbits (p p p = 0.01) and the ratio of villus height to crypt depth (p = 0.02 and p = 0.01) in neonatal rabbits were elevated in all DA-supplemented treatments, while a linear and quadratic effect was observed in jejunum, but a quadratic effect was observed in duodenum (p p p p = 0.04), zonula occludens-1 (ZO-1) (p p = 0.03), and solute carrier family 5 member 9 (SCL5A9) (p p p = 0.01, p = 0.04, and p p = 0.04, p = 0.04, and p = 0.03) epithelium were decreased in the DA170 and DA340 groups (p p < 0.05). In summary, as a functional additive, maternal DA supplementation with 170 and 340 mg/kg DA during lactation can promote the growth of neonatal rabbits, which is related to improved antioxidative capacity and immunity, as well as improved intestinal health in neonatal rabbits

Downregulation of homeobox gene Barx2 increases gastric cancer proliferation and metastasis and predicts poor patient outcomes

Barx2 is a Bar family homeodomain transcription factor shown to play a critical role in cell adhesion and cytoskeleton remodeling, key processes in carcinogenesis and metastasis. Using quantitative real-time PCR, Western blotting, and immunohistochemistry, we found that Barx2 is expressed at lower levels in human gastric cancer (GC) tissues than in adjacent normal mucosa. In a multivariate analysis, Barx2 expression emerged as an independent prognostic factor for disease-free and overall survival. Kaplan-Meier survival analysis showed a trend toward even shorter overall survival in the patient group with Barx2-negative tumors, independent of advanced UICC stage and tumor relapse. Using in vitro and in vivo assays, we demonstrated that under normal conditions Barx2 inhibited GC cell proliferation and invasiveness through inhibition of the Wnt/beta-catenin signaling pathway. These findings indicate that reduction or loss of Barx2 dis-inhibits GC cell proliferation and invasion, and that reduction in Barx2 could serve as an independent prognostic biomarker for poor outcome in GC patients.Funding Agencies|National Natural Science Foundation of China [81272750]</p

Down-regulation of Barx2 predicts poor survival in colorectal cancer

Human BarH-like homeobox 2 (Barx2), a homeodomain factor of the Bar family, has an important role in controlling the expression of cell adhesion molecules and has been reported in an increasing array of tumor types except colorectal cancer (CRC). The purpose of the current study was to characterize the expression of Barx2 and assess the clinical significance of Barx2 in CRC. First, we analyzed the expression of Barx2 in two independent public datasets from Oncomine. Subsequently, we evaluated Barx2 mRNA and protein expression by quantitative real-time PCR and western blotting, respectively. It was determined that Barx2 expression was lower in tumor tissues than in adjacent non-tumorous colorectal tissues of CRC patients, consistent with results from the public datasets. Subsequently, a tissue microarray containing 196 CRC specimens was evaluated for Barx2 expression by immunohistochemical staining. It was found that low expression of Barx2 significantly correlated with TNM stage, AJCC stage, differentiation, and relapse in patients with CRC. Patients with lower levels of Barx2 expression showed reduced disease-free survival and overall survival. Furthermore, a trend toward shorter overall survival in the patient group with Barx2-negative tumors independent of advanced AJCC stage and poor differentiation was determined by Kaplan-Meier survival analysis. Based on univariate and multivariate analyses, Barx2 expression was an independent prognostic factor for determining CRC prognosis. Taken together, low Barx2 expression was associated with the progression of CRC and could serve as a potential independent prognostic biomarker for patients with CRC. (C) 2016 The Authors. Published by Elsevier Inc.Funding Agencies|National Natural Science Foundation of China [81272750]</p

miR-181a-5p promotes the progression of gastric cancer via RASSF6-mediated MAPK signalling activation

We previously discovered that Ras association domain family member 6 (RASSF6) was downregulated and predicted poor prognosis in GC patients. However, the mechanisms of the down regulation of RASSF6 in GC remained unclear. Increasing evidence indicates that dysregulation of microRNAs promotes the progression of cancer through the repression of tumour suppressors. Here, we identified miR-181a-5p as a novel regulator of RASSF6 in GC. Functionally, ectopic expression or silencing of miR-181a-5p, respectively, promoted or inhibited GC cell proliferation, colony formation and cell cycle transition, as well as enhanced or prevented the invasion, metastasis of GC cells and epithelial to mesenchymal transition of GC cells in vitro and in vivo. Molecularly, miR-181a-5p functioned as an onco-miRNA by activating the RASSF6-regulated MAKP pathway. Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. Clinically, high miR-181a-5p expression predicted poor survival in GC patients, especially combined with low RASSF6 expression. Collectively, we identified miR-181a-5p as an onco-miRNA, which acts by directly repressing RASSF6 in GC. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.Funding Agencies|National High Technology Research and Development Program of China [SS2014AA020803]; National Natural Science Foundation of China [81272750, 81302083]</p

miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGF beta-mediated epithelial to mesenchymal transition

Background: Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression. Methods: qPCR and in situ hybridization were used to evaluate the expression of miR-4775 in 544 pairs of paraffin-embedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemical staining was applied to investigate the expression of miR-4775-regulated Smad7/TGF beta pathway-associated markers. In vitro and in vivo invasion and metastasis assays were used to explore the function of miR-4775 in the progression of CRC. Results: miR-4775 was identified as a high-risk factor for CRC metastasis and recurrence, with high levels predicting poor survival among the 544 studied CRC patients. Furthermore, high miR-4775 expression promoted the invasion of CRC cells as well as metastasis and the epithelial to mesenchymal transition (EMT) via Smad7-mediated activation of TGF beta signaling both in vitro and in vivo. Downregulating miR-4775 or overexpressing Smad7 reversed the tumor-promoting roles of miR-4775/ Smad7/TGF beta in vitro and in vivo. Conclusion: miR-4775 promotes CRC metastasis and recurrence in a Smad7/TGF beta signaling-dependent manner, providing a new therapeutic target for inhibiting the metastasis or recurrence of the disease.Funding Agencies|National High Technology Research and Development Program of China [SS2014AA020803]; National Natural Science Foundation of China [81220108021, 81302083, 81272750]; Natural Science Foundation of Shanghai [16ZR1427700]; Project of Shanghai Science and Technology Commission [124119a1700, 14411950502]; Project of Songjiang District [0702 N14001]</p