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SMURF1-mediated ubiquitination of ARHGAP26 promotes ovarian cancer cell invasion and migration
Xuri Chen,Shaoyun Chen,Yao Li,Yanling Gao,Shuying Huang,Hongping Li,Yuanfang Zhu 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
Rho GTPase-activating protein 26 (ARHGAP26) is a negative regulator of the Rho family that converts the small GTPbinding protein RhoA (GTP-RhoA) to its inactive GDP-bound form and is a putative tumor suppressor gene associated with cell growth and migration. Here, the involvement of ARHGAP26 in ovarian cancer cell proliferation and migration was investigated. In this study, low ARHGAP26 expression was observed in ovarian cancer tissues and was associated with a poor overall survival and higher β-catenin expression in patients with ovarian cancer. A2780 and HEY cells with ARHGAP26 upregulation showed decreased cell proliferation, migration, and invasion, along with decreased GTPRhoA, β-catenin, VEGF, MMP2, and MMP7 expression. ARHGAP26 upregulation in A2780 cells also inhibited lung metastasis in vivo. SKOV3 cells with ARHGAP26 downregulation demonstrated an inverse effect, which was inhibited by ARHGAP26 overexpression or DKK1, an antagonist of the β-catenin pathway. SMURF1, an E3 ubiquitin ligase, interacted with and induced ubiquitination of ARHGAP26. ARHGAP26 upregulation in SKOV3 cells significantly inhibited SMURF1 upregulation-induced cell migration and invasion. Overall, SMURF1-mediated ubiquitination of ARHGAP26 may promote invasion and migration of ovarian cancer cells via the β-catenin pathway.
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Yang, Qian,Cai, Xixi,Huang, Muchen,Jia, Lee,Wang, Shaoyun Royal Society of Chemistry 2019 Food & Function Vol.10 No.6
<P><I>Pseudostellaria heterophylla</I> has been becoming a popular research topic because of its functionally active components. The immunomodulatory activity of <I>P. heterophylla</I> peptide (PPH) derived from protein hydrolysate and the molecular mechanism underlying its immunomodulatory effect were investigated in this study. Immunomodulatory PPH achieved the highest stimulation index of 1.53 at a concentration of 100 μg mL<SUP>−1</SUP> for 48 h in spleen lymphocytes and promoted the secretions of tumor necrosis factor-α, interferon-γ, and interleukin-10. Moreover, PPH could elevate the intracellular Ca<SUP>2+</SUP> concentration, calcineurin activity and nuclear factor of activated T cell (NFAT) c1 mRNA expression. Meanwhile these effects could be diminished by the treatment of verapamil and cyclosporin A, suggesting that PPH may activate spleen lymphocytes <I>via</I> the Ca<SUP>2+</SUP>/CaN/NFATc1/IFN-γ signaling pathway. These findings demonstrate that the <I>P. heterophylla</I> peptide has the potential to be utilized as a nutraceutical supplement to strengthen the immune system in the human body.</P>
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Yang Zou,Tao Zhang,Guannan Wang,Mengwen Zhou,Yabo Xiong,Shaoyun Huang,Houbin Li,Xinghai Liu 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.82 No.-
3,3,7,7-tetrakis(difluoroamino) octahydro-1,5-dinitro-1,5-diazocine (HNFX) is a high-density energeticoxidizer with four difluoroamino groups (-NF2). In this study, 1,5-ditosyl-1,5-diazocane-3,7-dione, as animportant intermediate for synthesis of HNFX, was successfully synthesized using Swern oxidation in atraditional batch reactor and a continuousflow microreactor, respectively. 1,5-dotosyl-1,5-diazocane-3,7-dione was characterized by HPLC, FTIR, 1H NMR, 13C NMR, Mass spectrometry, and X-ray crystaldiffraction. Compared with the traditional batch reactor, the microreactor showed several advantages,including less reaction time, milder reaction temperature, higher yield and selectivity for 1,5-ditosyl-1,5-diazocane-3,7-dione. Moreover, the microreactor could ensure the safer and large-scale industrialproduction of 1,5-ditosyl-1,5-diazocane-3,7-dione. However, some solids produced in Swern oxidationwhich might block the channels (diameter of 0.3 mm) in the microreactor. To overcome the challenges,the experimental device was modified to suit for Swern oxidation, contributing to wider application ofthe microreactor. Besides, response surface methodology (RSM) was introduced and an appropriatemathematical model was built to optimize experimental conditions. The optimum experimentalparameters were recommended as 7.8 C for the reaction temperature, 7.7 mL/min for theflow rate, and6% for the concentration of oxalyl chloride. The actual yield of 1,5-ditosyl-1,5-diazocane-3,7-dione was89.7%, which was in great agreement with the highest predicted yield (90.1%).
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