DPYSL2 as potential diagnostic and prognostic biomarker linked to immune infiltration in lung adenocarcinoma.

BACKGROUND: Dihydropyrimidinase like 2 (DPYSL2) has been linked to tumor metastasis. However, the function of DPSY2L in lung adenocarcinoma (LUAD) is yet to be explored. METHODS: Herein, we assessed DPYSL2 expression in various tumor types via online databases such as Oncomine and Tumor Immune Estimation Resource (TIMER). Further, we verified the low protein and mRNA expressions of DPYSL2 in LUAD via the ULCAN, The TCGA and GEPIA databases. We applied the ROC curve to examine the role of DPYSL2 in diagnosis. The prognostic significance of DPYSL2 was established through the Kaplan-Meier plotter and the Cox analyses (univariate and multivariate). TIMER was used to explore DPYSL2 expression and its connection to immune infiltrated cells. Through Gene Set Enrichment Analysis, the possible mechanism of DPYSL2 in LUAD was investigated. RESULTS: In this study, database analysis revealed lower DPYSL2 expression in LUAD than in normal tissues. The ROC curve suggested that expression of DPYSL2 had high diagnostic efficiency in LUAD. The DPYSL2 expression had an association with the survival time of LUAD patients in the Kaplan-Meier plotter and the Cox analyses. The results from TIMER depicted a markedly positive correlation of DPYSL2 expression with immune cells infiltrated in LUAD, such as macrophages, dendritic cells, CD4+ T cells, and neutrophils. Additionally, many gene markers for the immune system had similar positive correlations in the TIMER analysis. In Gene Set Enrichment Analysis, six immune-related signaling pathways were associated with DPYSL2. CONCLUSIONS: In summary, DPYSL2 is a novel biomarker with diagnostic and prognostic potential for LUAD as well as an immunotherapy target. HIGHLIGHTS: 1. Expression of DPYSL2 was considerably lower in LUAD than in normal tissues. 2. Investigation of multiple databases showed a high diagnostic value of DPYSL2 in LUAD. 3. DPYSL2 can independently predict the LUAD outcomes. 4. Immune-related mechanisms may be potential ways for DPYSL2 to play a role in LUAD.

LncRNA SNHG1 promotes EMT process in gastric cancer cells through regulation of the miR-15b/DCLK1/Notch1 axis.

BACKGROUND: Gastric cancer (GC) is a malignant tumour originating from the gastric mucosa epithelium that seriously threatens human health. DCLK1, miR-15b and lncRNA SNHG1 play potential roles in the occurrence of GC, but the mechanism remains unclear. METHODS: Gene expression of DCLK1, miR-15b and lncRNA SNHG1 was investigated by qRT-PCR. Protein expression was detected by Western blotting. Migration and invasion of gastric cancer cells was tested by a Transwell assay and wound healing assay. Cell proliferation was measured by an MTT assay. Finally, the correctness of the prediction results was confirmed by a dual-luciferase reporter assay. RESULTS: The expression of DCLK1, Notch1, and SNHG1 was increased in GC tissues, while the expression of miR-15b was decreased. Overexpression of lncRNA SNHG1 promoted the expression of DCLK1 and Nothc1 in GC cells. Moreover, miR-15b targeted DCLK1 to regulate Notch1 expression and inhibited the EMT process in GC cells. SNHG1 enhanced the effects of DCLK1/Notch1 on the EMT process through regulating miR-15b expression. CONCLUSION: SNHG1 enhances the EMT process in GC cells through DCLK1-mediated Notch1 pathway, which can be a potential target for treating GC.

MiR-185-3p regulates epithelial mesenchymal transition via PI3K/Akt signaling pathway by targeting cathepsin D in gastric cancer cells.

BACKGROUND: Recently research reported that miR-185-3p could serve as an independent prognosis factor in gastric cancer (GC). However, the functional role and underlying mechanism of miR-185-3p in GC and epithelial-mesenchymal transition (EMT) progression remains largely elusive. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to analyze the expression of miR-185-3p and cathepsin D in patient-derived GC samples and various GC cell lines. Scratch assay and Transwell assay were used to evaluate the migration ability. The influence of miR-185-3p on the cell cycle distribution and cell apoptosis was evaluated using flow cytometry. Western blotting assay was performed to detect the expression of EMT associated proteins and the activity of PI3K/Akt signaling pathway. Furthermore, the interaction between miR-185-3p and cathepsin D was explored by dual-luciferase reporter assay. RESULTS: Our data revealed that miR-185-3p was down-regulated, while cathepsin D was up-regulated in both patient-derived GC samples and GC cells. Apart from inducing apoptosis, overexpression of miR-185-3p also inhibited EMT process and migration of GC cells. Mechanically, we firstly verified that miR-185-3p directly targeted the cathepsin D. Furthermore, miR-185-3p exerted its function on EMT process and migration via inhibiting cathepsin D to mediated PI3K/Akt signaling pathway. CONCLUSIONS: Our findings suggested that miR-185-3p targeted cathepsin D inhibiting EMT process via PI3K/Akt signaling, which may serve as a potential prognosis factor and therapeutic target to reduce the malignancy of GCs.

E3 ubiquitin ligase SOR1 regulates ethylene response in rice root by modulating stability of Aux/IAA protein.

Plant hormones ethylene and auxin synergistically regulate plant root growth and development. Ubiquitin-mediated proteolysis of Aux/IAA transcriptional repressors by the E3 ubiquitin ligase SCFTIR1/AFB triggers a transcription-based auxin signaling. Here we show that rice (Oryza sativa L.) soil-surface rooting 1 (SOR1), which is a RING finger E3 ubiquitin ligase identified from analysis of a rice ethylene-insensitive mutant mhz2/sor1-2, controls root-specific ethylene responses by modulating Aux/IAA protein stability. SOR1 physically interacts with OsIAA26 and OsIAA9, which are atypical and canonical Aux/IAA proteins, respectively. SOR1 targets OsIAA26 for ubiquitin/26S proteasome-mediated degradation, whereas OsIAA9 protects the OsIAA26 protein from degradation by inhibiting the E3 activity of SOR1. Auxin promotes SOR1-dependent degradation of OsIAA26 by facilitating SCFOsTIR1/AFB2-mediated and SOR1-assisted destabilization of OsIAA9 protein. Our study provides a candidate mechanism by which the SOR1-OsIAA26 module acts downstream of the OsTIR1/AFB2-auxin-OsIAA9 signaling to modulate ethylene inhibition of root growth in rice seedlings.

Folate status and colorectal cancer risk: A 2016 update.

The consensus of epidemiologic evidence indicates that an abundant intake of foodstuffs rich in folate conveys protection against the development of colorectal cancer, and perhaps some other common cancers as well. Pre-clinical models substantiate that the relationship is a genuinely causal one. Pre-clinical models have also lent mechanistic insights into the biochemical and molecular pathways by which adequate folate exposure conveys these protective effects, and human studies are beginning to confirm the relevance of this mechanistic understanding to human cancer biology. Enhancement of genetic stability appears to be a major mechanism by which folate sufficiency protects against carcinogenesis. To date, the Wnt signaling cascade has been the pathway most examined in this regard. The relationship between folate exposure and colorectal cancer risk is a complex one, in part because a number of extrinsic and intrinsic factors act as effect modifiers. This review discusses how the intake of the other three B-vitamins integral to the 1-carbon pathway acts as one such effect modifier. In addition, two concepts that remain matters of considerable debate are whether parental intake of folate impacts on subsequent cancer risk in the offspring, and whether excessive intakes of folate may have a paradoxical cancer-promoting effect: observations underlying these two concepts are presented as well.

Casticin, a flavonoid, potentiates TRAIL-induced apoptosis through modulation of anti-apoptotic proteins and death receptor 5 in colon cancer cells.

We investigated the effect of casticin on apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). We found that casticin potentiated TRAIL-induced apoptosis in human colon cancer cells. Casticin downregulated cell survival proteins including Bcl-xL, Bcl-2, survivin, XIAP and cFLIP, and induced death receptor 5 (DR5), but had no effect on DR4 and decoy receptors (DcR1 or DcR2). Deletion of DR5 by siRNA significantly reduced the apoptosis induced by TRAIL and casticin. In addition, casticin induced reactive oxygen species (ROS) generation in a dose-dependent manner. Collectively, the present study showed that casticin potentiates TRAIL-induced apoptosis through downregulation of cell survival proteins and induction of DR5 mediated by ROS.

Generation of glyco-engineered BY2 cell lines with decreased expression of plant-specific glycoepitopes.

Plants are known to be efficient hosts for the production of mammalian therapeutic proteins. However, plants produce complex N-glycans bearing ß1,2-xylose and core α1,3-fucose residues, which are absent in mammals. The immunogenicity and allergenicity of plant-specific Nglycans is a key concern in mammalian therapy. In this study, we amplified the sequences of 2 plant-specific glycosyltransferases from Nicotiana tabacum L. cv Bright Yellow 2 (BY2), which is a well-established cell line widely used for the expression of therapeutic proteins. The expression of the endogenous xylosyltranferase (XylT) and fucosyltransferase (FucT) was downregulated by using RNA interference (RNAi) strategy. The xylosylated and core fucosylated N-glycans were significantly, but not completely, reduced in the glycoengineered lines. However, these RNAi-treated cell lines were stable and viable and did not exhibit any obvious phenotype. Therefore, this study may provide an effective and promising strategy to produce recombinant glycoproteins in BY2 cells with humanized N-glycoforms to avoid potential immunogenicity.

[Somatic hybrids between Rorippa indica (Linn.) Hiern and Brassica napus L. through protoplast-fusion system].

High yield of protoplast isolation was achieved from hypocotyls of B. napus L. and leaves of Rorippa indica (Linn.) Hiern. The isolated protoplasts were used to establish an efficient protoplast-fusion system between the two cruciferous species by PEG-DMSO method and culturing with MS liquid medium. Ten somatic fusion hybrids between B. napus and R. indica were obtained. The enzyme combinations for isolating protoplast from B. napus L. and R. indica were 1% cellulase + 0.2% macerozyme + 3 mmol/L MES and 0.25% cellulase + 0.5% macerozyme + 5 mmol/L MES, respectively. Fusion percentage of 10.4% was obtained on the condition of 30% PEG + 0.3 mol/L glucose +50 mmol/L CaCl2.2H2O + 15% DMSO. Seeds plants obtained from protoplast fusion are new germplasm derived from R. indica.