Down regulation of miR-30a-5p and miR-182–5p in gastric cancer: Clinical impact and survival analysis

Background and aimGastric Cancer (GC) is a leading cause of morbidity and mortality worldwide, particularly in developing nations, only a few suitable gastric cancer serum biomarkers with acceptable sensitivity and specificity exist. This work aims to highlight and uncover miR-30a-5p and miR-182–5p′s diagnostic roles regarding gastric cancer and their roles in predicting prognosis.Methods148 patients participated in this study. Groups I, II, and III had 47 patients with GC, 54 patients with benign gastric lesions, and 47 apparently healthy subjects of coincided age and gender as controls, respectively. All participants were clinically evaluated and subjected to CBC, serum CEA, and CA19-9 by ELISA, and real-time PCR tests of miR-30a-5p and miR-182–5p.ResultsMiR30a-5p and miR-182–5p were down regulated in gastric cancer patients in Group I more than Groups II and III (P < 0.001). ROC curve analysis revealed that miR30a-5p had better AUC, sensitivity, and specificity (0.961%, 93.62%, and 90.74%respectively). When miR-182–5p was gathered with CEA and CA19-9, specificity raised to 98.15% and PPV to 97.6%. Lower miR-30a-5p levels are linked with the presence of distant metastases, advanced TNM stage, and degree of pathological differentiation of tumors in GC patients (p = 0.034, 0.019, 0.049) respectively. According to the multivariate analysis, miR30a-5p expression level could be an independent predictor of GC.ConclusionOur results exhibited that miRNAs, miR-30a-5p and miR182–5p, gene expression have a diagnostic power and can identify patients with GC. MiR-30a-5p displayed the highest diagnostic specificity and sensitivity. Besides other known tumor markers, they could offer simple noninvasive biomarkers that predict gastric cancer.     

MTHFD2 promotes tumorigenesis and metastasis in lung adenocarcinoma by regulating AKT/GSK-3β/β-catenin signalling

Recent studies have demonstrated that one-carbon metabolism plays a significant role in cancer development. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme of one-carbon metabolism, has been reported to be dysregulated in many cancers. However, the specific role and mechanism of MTHFD2 in lung adenocarcinoma (LUAD) still remains unclear. In this study, we evaluated the clinicopathological and prognostic values of MTHFD2 in LUAD patients. We conducted a series of functional experiments in vivo and in vitro to explore novel mechanism of MTHFD2 in LUAD. The results showed that MTHFD2 was significantly up-regulated in LUAD tissues and predicted poor prognosis of LUAD patients. Knockdown of MTHFD2 dramatically inhibited cell proliferation and migration by blocking the cell cycle and inducing the epithelial-mesenchymal transition (EMT). In addition, MTHFD2 knockdown suppressed LUAD growth and metastasis in cell-derived xenografts. Mechanically, we found that MTHFD2 promoted LUAD cell growth and metastasis via AKT/GSK-3β/β-catenin signalling. Finally, we identified miR-30a-3p as a novel regulator of MTHFD2 in LUAD. Collectively, MTHFD2 plays an oncogenic role in LUAD progression and is a promising target for LUAD diagnosis and therapy.     

Expression,SNV identification,linkage disequilibrium,and combined genotype association analysis of the muscle-specific gene CSRP3 in Chinese cattle

The cysteine and glycine-rich protein 3 (CSRP3) plays an important role in the myofiber differentiation. Here, we identified five SNVs in all exon and intron regions of the CSRP3 gene using DNA sequencing, PCR-RFLP and forced-PCR-RFLP methods in 554 cattle. Four of the five SNVs were significantly associated with growth performance and carcass traits of the cattle. In addition, we evaluated haplotype frequency and linkage disequilibrium coefficient of five sequence variants. The result of haplotype analysis demonstrated 28 haplotypes present in Qinchuan and two haplotypes in Chinese Holstein. Only haplotypes 1 and 8 were being shared by two populations, haplotype 14 had the highest haplotype frequency in Qinchuan (17.4%) and haplotype 8 had the highest haplotype frequency in Chinese Holstein (94.4%). Statistical analyses of combined genotypes indicated that some combined genotypes were significantly or highly significantly associated with growth and carcass traits in the Qinchuan cattle population. qPCR analyses also showed that bovine CSRP3 gene was exclusively expressed in longissimus dorsi muscle and heart tissues. The data support the high potential of the CSRP3 as a marker gene for the improvement of growth performance and carcass traits in selection programs.     

Analysis of quantitative trait loci affecting chlorophyll content of rice leaves in a double haploid population and two backcross populations

Chlorophyll content, one of the most important physiological parameters related to plant photosynthesis, is usually used to predict yield potential. To map the quantitative trait loci (QTLs) underlying the chlorophyll content of rice leaves, a double haploid (DH) population was developed from an indica/japonica (Zhenshan 97/Wuyujing 2) crossing and two backcross populations were established subsequently by backcrossing DH lines with each of their parents. The contents of chlorophyll a and chlorophyll b were determined by using a spectrophotometer to directly measure the leaf chlorophyll extracts. To determine the leaf chlorophyll retention along with maturation, all measurements were performed on the day of heading and were repeated 30 days later. A total of 60 QTLs were resolved for all the traits using these three populations. These QTLs were distributed on 10 rice chromosomes, except chromosomes 5 and 10; the closer the traits, the more clustering of the QTLs residing on common rice chromosomal regions. In general, the majority of QTLs that specify chlorophyll a content also play a role in determining chlorophyll b content. Strangely, chlorophyll content in this study was found mostly to be lacking or to have a negative correlation with yield. In both backcross F₁ populations, overdominant (or underdominant) loci were more important than complete or partially dominant loci for main-effect QTLs and epistatic QTLs, thereby supporting previous findings that overdominant effects are the primary genetic basis for depression in inbreeding and heterosis in rice.     

The PGRS domain is responsible for translocation of PE_PGRS30 to cell poles while the PE and the C-terminal domains localize it to the cell wall

PE_PGRS proteins localize in the mycobacterial cell wall and the cell wall localization of PE_PGRS33 has been shown to be attributed to its PE domain. In this study, we expressed deletion mutants of PE_PGRS30 in Mycobacterium smegmatis to characterize the role of its domains in protein localization. It was revealed that, apart from the PE domain, the C-terminal domain present in few PE_PGRS proteins carries individual cell wall localization signals. Proteinase K sensitivity assay showed that PE_PGRS30 is exposed on the mycobacterial surface through its PGRS domain. PGRS domain was also shown to be responsible for polar localization of PE_PGRS30.     

Effects of acidic-astressin and ovine-CRF microinfusions into the ventral hippocampus on defensive behaviors in rats

This study investigated a possible role for ventral hippocampal corticotropin-releasing factor (CRF) in modulating both unconditioned and conditioned defensive behaviors by examining the effects of pre-training ventral hippocampal ovine-CRF (oCRF) or acidic-astressin ([Glu^11,16]Ast) microinfusions in male Long-Evans hooded rats exposed to various threat stimuli including the elevated plus-maze (EPM) (oCRF), cat odor (oCRF and [Glu^11,16]Ast) and a live cat ([Glu^11,16]Ast). Unconditioned defensive behaviors were assessed during threat exposure, while conditioned defensive behaviors were assessed in each predator context 24 h after the initial threat encounter. Pre-training infusions of the CRF₁ and CRF₂ receptor agonist oCRF significantly increased defensive behaviors during both the unconditioned and conditioned components of the cat odor test, as well as exposure to the EPM. In contrast to the behavioral effects of oCRF microinfusions, the CRF₁ and CRF₂ receptor antagonist [Glu^11,16]Ast significantly decreased defensive behaviors during exposure to cat odor, while producing no discernible effects following a second injection in the cat exposure test. During conditioned test trials, pre-training infusions of [Glu^11,16]Ast also significantly reduced defensive behaviors during re-exposure to both predator contexts. These results suggest a specific role for ventral hippocampal CRF receptors in modulating anxiety-like behaviors in several ethologically relevant animal models of defense.     

Comparative analysis of her genes during fish somitogenesis suggests a mouse/chick-like mode of oscillation in medaka

Somitogenesis is the key developmental step, which divides the vertebrate body axis into segmentally repeated structures. It requires an intricate process of pre-patterning, which is driven by an oscillator mechanism consisting of the Delta–Notch pathway and various hairy- and Enhancer of split-related (her) genes. The subset of her genes, which are necessary to set up the segmentation clock, reveal a complex scenario of interactions. To understand which her genes are essential core players in this process, we compared the expression patterns of somitogenesis-relevant her genes in zebrafish and medaka (Oryzias latipes). Most of the respective medaka genes (Ol-her) are duplicated like what has been shown for zebrafish (Dr-her) and pufferfish genes (Fr-her). However, zebrafish genes show some additional copies and significant differences in expression patterns. For the paralogues Dr-her1 and Dr-her11, only one copy exists in the medaka (Ol-her1/11), which combines the expression patterns found for both zebrafish genes. In contrast to Dr-her5, the medaka orthologue appears to play a role in somitogenesis because it is expressed in the presomitic mesoderm (PSM). PSM expression also suggests a role for both Ol-her13 genes, homologues of mouse Hes6 (mHes6), in this process, which would be consistent with a conserved mHes6 homologue gear in the segmentation clock exclusively in lower vertebrates. Members of the mHes5 homologue group seem to be involved in somite formation in all vertebrates (e.g. Dr- and Ol-her12), although different paralogues are additionally recruited in zebrafish (e.g. Dr-her15) and medaka (e.g. Ol-her4). We found that the linkage between duplicates is strongly conserved between pufferfish and medaka and less well conserved in zebrafish. Nevertheless, linkage and orientation of several her duplicates are identical in all three species. Therefore, small-scale duplications must have happened before whole genome duplication occurred in a fish ancestor. Expression of multiple stripes in the intermediate PSM, characteristic for the zebrafish orthologues, is absent in all somitogenesis-related her genes of the medaka. In fact, the expression mode of Ol-her1/11 and Ol-her5 indicates dynamism similar to the hairy clock genes in chicken and mouse. This suggests that Danio rerio shows a rather derived clock mode when compared to other fish species and amniotes or that, alternatively, the clock mode evolved independently in zebrafish, medaka and mouse or chicken.An erratum to this article can be found at