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        SOX11-dependent CATSPER1 expression controls colon cancer cell growth through regulation the PI3K/AKT signaling pathway

        Huang Yang,Wang Yicheng,Wu Zhongmei,Li Tao,Li Shupei,Wang Chan,Ao Jine,Yang Changming,Zhou Yu 한국유전학회 2022 Genes & Genomics Vol.44 No.11

        Background: Colorectal cancer (CRC) is one of the most common malignant tumors and the fourth leading cause of cancer death worldwide. Constitutive activation of the PI3K/AKT signaling pathway is a hallmark of colon tumor growth. CATSPER1 gene encodes a pore-forming and pH-sensing subunit of the CatSper Ca2+-permeable channel, a sperm-specific calcium channel essential for hyperactivated motility and male fertility. However, the function of CATSPER1 outside the male reproductive system is unclear. Objective: This study was designed to explore whether CatSper exerted its functional role in the progress of CRC, and investigate the possible mechanisms. Methods: Microarray data (GSE146587) from 6 patients diagnosed with stage III CRC post-surgery was analyzed by Limma R package. The Kaplan Meier plotter (KM plotter) database was used to assess the relevance of CATSPER1 mRNA expression to the overall survival (OS) rates in CRC. Western blot, real-time PCR and luciferase reporter assays were used to determine the SOX11-CATSPER1 axis in CRC cells. Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate CATSPER1 knockout (KO) CRC cells. The proliferation of CRC cells was determined by BrdU incorporation and colony formation assays. The effect of CATSPER1 on CRC tumor growth in vivo was investigated in a mice tumor xenograft model. Results: Here, we show that CATSPER1 expression was significantly up-regulated in CRC and elevated CATSPER1 was associated with poor overall survival (OS). Moreover, the transcription factor SOX11 (SRY-related high-mobility-group (HMG) box 11) activated CATSPER1 transcription in CRC cells. Functionally, we showed that CATSPER1 promoted CRC cells proliferation both in vitro and in vivo. At the molecular level, we demonstrated that CATSPER1 might maintain CRC malignant process partly through the activation of the PI3K/AKT signaling pathway. Conclusion: Increased CATSPER1 expression facilitates CRC cells proliferation, suggesting that targeting CATSPER1 might represent a promising strategy for colon cancer treatment.

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        The Protective Roles of S-adenosylmethionine Decarboxylase (SAMDC) Gene in Melon Resistance to Powdery Mildew Infection

        Changming Liu,Xiaoling Li,Ruiping Yang,Yanling Mo,Yongqi Wang,Feng Xian,Xian Zhang,Fei Wang 한국원예학회 2014 Horticulture, Environment, and Biotechnology Vol.55 No.6

        Powdery mildew caused by Podosphaera xanthii (P. xanthii) is one of important diseases in melon. Wehave previously investigated the differential gene expression in the incompatible P. xanthii-melon interactions andidentified one EST containing homologous sequences to S-adenosylmethionine decarboxylase (SAMDC) cDNA. Giventhis, SAMDC gene of Cucumis melo was cloned and designated as CmSAMDC in this study. It was 1,095 bp longand encoded a 364-amino acid peptide with a molecular mass of 40 kD. By sequence analyzing, the deducedCmSAMDC protein was shown to have two conserved regions of a putative proenzyme cleavage site and a PESTdomain. In addition, the expressions of CmSAMDC in the resistant melon materials increased more sharply than inthe susceptible the melon materials, and the higher polyamines (PAs) and hydrogen peroxide (H2O2) contents inresistant melon materials were found as well, which were accompanied by up-regulation of the stress-responsive defenseenzyme activities. Over-expression of CmSAMDC in Arabidopsis resulted in greatly reduced pathogen infection in theinoculated leaves of transgenic lines, enhanced resistance to powdery mildew, and the enhanced resistance appearedto be associated with pathogen-induced cell death. Taken together, our results suggested that CmSAMDC and perhapsits orthologous genes might be involved in responses of plants to biotrophic pathogens.

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