Long noncoding RNA LINC01234 promoted cell proliferation and invasion via miR-1284/TRAF6 axis in colorectal cancer

Colorectal cancer is one of the most common and leading malignancies globally. Long noncoding RNAs (lncRNAs) function as potentially critical regulator in colorectal cancer. LINC01234, a novel lncRNA in tumor biology, regulates the progression of various tumors. However, the tumorigenic mechanism of LINC01234 in colorectal cancer is still unclear. This study was performed with the aim to prospectively investigate clinical significance, effect, and mechanism of lncRNA LINC01234 in colorectal cancer. First, we found that LINC01234, localized in the cytoplasm, was increased in both colorectal cancer cell lines and tissues. Subsequent functional assays suggested LINC01234 knockdown suppressed cell proliferation, migration, and invasion of colorectal cancer cells, while blocked cell cycle and induced cell apoptosis. Moreover, we identified that miR-1284 was target of LINC01234, we further demonstrated a negative correlation with LINC01234 in colorectal cancer tissues and cells. Furthermore, miR-1284 targeted and suppressed tumor necrosis factor receptor–associated factor 6 (TRAF6). Loss-of-function assay revealed that LINC01234 silencing suppressed colorectal cancer progression through inhibition of miR-1284. In vivo subcutaneous xenotransplanted tumor model indicated LINC01234 knockdown inhibited in vivo tumorigenic ability of colorectal cancer via downregulation of TRAF6. Collectively, this study clarified the biological significance of LINC01234/miR-1284/TRAF6 axis in colorectal cancer progression, providing insights into LINC01234 as novel potential therapeutic target for colorectal cancer therapeutic from bench to clinic.     

Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons

In our previous experiments, evidence of free radical formation has been demonstrated in gerbil brain after kainic acid (KA) administration. In the present study, the mechanisms involved in KA-induced free radical formation and subsequent cell degeneration were investigated using high density cortical neuron cultures. A free radical trapping agent,a-phenyl-N-tert-butyl-nitrone (PBN), as well as the combined action of superoxide dismutase and catalase attenuated KA neurotoxic effect. Calpain-induced xanthine oxidase (XO) activation may play an important role in KA excitotoxicity since calpain inhibitor I as well as allopurinol, a selective XO inhibitor, significantly protected the cortical neurons from KA-induced cell death. However, XO activation may not be the only source producing free radicals, other free radical generating systems such as nitric oxide synphase may also play a role in KA insult.     

Large scale purification of myo-inositol monophosphate phosphatase from porcine brains

myo-Inositol monophosphate phosphatase (IMPase) has been purified 888-fold to apparent homogeneity from procine brains. The purification procedure involves: homogenization, ammonium sulfate fractionation, and a number of ion-exchange and gel-filtration chromatography steps. The purified enzyme exhibited a final specific activity of 932 nmol . min(-1) . mg(-1). The molecular mass of the enzyme was estimated to be 29kDa by SDS poly-acrylamide gel electrophoresis and 58 +/- 5 kDa by HPLC gel filtration in 10mM Tris-HCI, pH 7.4. Kinetic measurements have shown that the apparent K(m) value of the phosphatase for the utilization of inositol-1-phosphate and beta-glycerol phosphate are 3.20 x 10(-4) and 8 x 10(-3) M, respectively. Similar to the same enzyme isolated from bovine brains, the porcine brain enzyme has been shown to be inhibited by lithium. The K(1) was determined to be 6.38 x 10(-4) M and the inhibition is uncompetitive. (c) 1995 John Wiley & Sons, Inc.     

Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 in gastric cancer

High levels of SOX4 expression have been found in a variety of human cancers, such as lung, brain and breast cancers. However, the expression of SOX4 in gastric tissues remains unknown. The SOX4 expression was detected using immunohistochemical staining and semi-quantitative RT-PCR, and our results showed that SOX4 was up-regulated in gastric cancer compared to benign gastric tissues. To further elucidate the molecular mechanisms underlying up-regulation of SOX4 in gastric cancers, we analyzed the expression of microRNA-129-2 (miR-129-2) gene, the epigenetic repression of which leads to overexpression of SOX4 in endometrial cancer. We found that up-regulation of SOX4 was inversely associated with the epigenetic silencing of miR-129-2 in gastric cancer, and restoration of miR-129-2 down-regulated SOX4 expression. We also found that inactivation of SOX4 by siRNA and restoration of miR-129-2 induced apoptosis in gastric cancer cells.     

Regulation of cystic fibrosis transmembrane regulator trafficking and protein expression by a Rho family small GTPase TC10

The cystic fibrosis transmembrane conductance regulator (CFTR)-interacting protein, CFTR-associated ligand (CAL) down-regulates total and cell surface CFTR by targeting CFTR for degradation in the lysosome. Here, we report that a Rho family small GTPase TC10 interacts with CAL. This interaction specifically up-regulates CFTR protein expression. Co-expression of the constitutively active form, TC10Q75L, increases total and cell surface CFTR in a dose-dependent fashion. Moreover, co-expression of the dominant-negative mutant TC10T31N causes a dose-dependent reduction in mature CFTR. The effect of TC10 is independent of the level of CFTR expression, because a similar effect was observed in a stable cell line that expresses one-tenth of CFTR. Co-expression of TC10Q75L did not have a similar effect on the expression of plasma membrane proteins such as Frizzled-3 and Pr-cadherin or cytosolic proteins such as tubulin and green fluorescent protein. TC10Q75L also did not have a similar effect on the vesicular stomatitis virus glycoprotein. Co-expression of constitutively active and dominant-negative forms of Cdc42 or RhoA did not affect CFTR expression in a manner similar to TC10, indicating that the effect of TC10 is unique within the Rho family. Metabolic pulse-chase experiments show that TC10 did not affect CFTR maturation, suggesting that it exerts its effects on the mature CFTR. Importantly, TC10Q75L reverses CAL-mediated CFTR degradation, suggesting that TC10Q75L inhibits CAL-mediated degradation of CFTR. TC10Q75L does not operate by reducing CAL protein expression or its ability to form dimers or interact with CFTR. Interestingly, the expression of TC10Q75L causes a dramatic redistribution of CAL from the juxtanuclear region to the plasma membrane where the two molecules overlap. These data suggest that TC10 regulates both total and plasma membrane CFTR expression by interacting with CAL. The GTP-bound form of TC10 directs the trafficking of CFTR from the juxtanuclear region to the secretory pathway toward the plasma membrane, away from CAL-mediated degradation of CFTR in the lysosome.     

Catch bonds: physical models, structural bases, biological function and rheological relevance

Force can shorten the lifetimes of macromolecular complexes (e.g., receptor-ligand bonds) by accelerating their dissociation. Perhaps paradoxical at first glance, bond lifetimes can also be prolonged by force. This counterintuitive behavior was named catch bonds, which is in contrast to the ordinary slip bonds that describe the intuitive behavior of lifetimes being shortened by force. Fifteen years after their theoretical proposal, catch bonds have finally been observed. In this article we review recently published data that have demonstrated catch bonds in the selectin system and suggested catch bonds in other systems, the theoretical models for their explanations, possible structural bases, their relation to flow-enhanced adhesion, and the potential biorheological relevance.