Project description:In this study, we showed that knockdown of CPSF6 inhibited GC cell growth and promoted apoptosis in vitro and in vivo. In order to understand the underlying mechanisms of CPSF6, we performed an APA profiling analysis in wild-type and CPSF6-knockdown AGS cells, using 3T-seq method.
Project description:In this study, we showed that CPSF6 promoted HCC cell growth, migration and metastasis in vitro and in vivo. In order to understand the underlying mechanisms of CPSF6, we aimed to perform a APA profiling analysis in hepatocyte and hepatoma carcinoma cells under different CPSF6 expression conditions using 3T-seq method.
Project description:We found that CPSF6, a component of the CFIm, can form liquid-liquid phase separation (LLPS) and the elevated LLPS induces the preferential usage of the distal poly(A) sites. CLK2, a kinase upregulated in cancer cells, destructs LLPS of CPSF6 by phosphorylating its arginine/serine-like domain. Albeit higher expression of CPSF6 in cancer, the reduction of LLPS leads to shortening 3’ UTR of cell cycle related genes and then promotes cell proliferation. These results reveal that LLPS regulation of CPSF6 is a fine tuning way of APA in cancer cells and provide a new mechanism for APA regulation by regulating LLPS of 3’ end processing factors through post-translational modification.
Project description:The aim of this study is to identify alterations induced in gastric mucosa of mice exposed to Pteridium aquilinum and/or infected with Helicobacter pylori, in order to identify genes that are induced by bracken fern exerts exacerbating effects on gastric lesions associated to the infection. Six groups of C57Bl/6 mice were be used: 1) control, 2) infected Helicobacter pylori, 3) treated with Bracken fern extract orogastrically, 4) treated with Bracken fern extract in drinking water, 5) infected Helicobacter pylori + treated with Bracken fern extract orogastrically, 6) infected Helicobacter pylori + treated with Bracken fern extract in drinking water. The infection procedure was performed using an orogastric inoculation of H.pylori (strain SS1) twice in the first week. The RNA isolation was done in triplicate (3 mice per each condition). Further evaluation of morphological alterations on gastric mucosa, proliferative index and induction of DNA strand breaks will be performed in the mice stomach exposed to Pteridium aquilinum infected or not with Helicobacter pylori. Alterations of glycosylation in gastric tissues will also evaluated.
Project description:Human embryonic stem cells (hESC) can be differentiated into progenitors resembling trophoblast upon exposure to BMP4. Putative trophpblast progenitors express APA cell surface marker Using FACS sorting and microarray we analysed the gene expression of APA-positive trophoblast progenitors, APA-negative progenitors and SSEA5-positive undifferentiated hESC and identified genes that contribute to the trophoblast fate
Project description:The aim of this study is to identify alterations induced in gastric mucosa of mice exposed to Pteridium aquilinum and/or infected with Helicobacter pylori, in order to identify genes that are induced by bracken fern exerts exacerbating effects on gastric lesions associated to the infection.
Project description:Cleavage factor I mammalian (CFIm) complex, composed of cleavage and polyadenylation specificity factor CPSF6, regulates alternative polyadenylation (APA). CPSF6 has a RS-like domain which plays role in protein -protein interactions. This interaction might have role in alternative polyadenylation site selection. The phosphorylation of RS- like domain might play role in protein -protein interaction and thus might have a role in alternative polyadenylation site selection. So we did mass specteroanalysis to analyse phosphorylation sites of RS-like domain of CPSF6.
Project description:A field for cancerization, or a field defect, is formed by the accumulation of genetic and epigenetic alterations in normal-appearing tissues, and is involved in various cancers, especially multiple cancers. Epigenetic alterations are frequently present in chronic inflammation-exposed tissues, but information on individual genes involved in the formation of a field defect is still fragmental. Here, using noncancerous gastric tissues of cancer patients, we isolated 16 aberrantly methylated genes, and identified chromatin remodelers ACTL6B and SMARCA1 as novel genes frequently methylated in non-cancerous tissues. SMARCA1 was expressed at high levels in normal gastric tissues, but was frequently silenced by aberrant methylation in gastric cancer cells. Moreover, somatic mutations of additional chromatin remodelers, such as ARID1A, SMARCA2, and SMARCA4, were found in 30% of gastric cancers. Mutant allele frequency suggested that the majority of cancer cells harbored a mutation when present. Depletion of a chromatin remodeler, SMARCA1 or SMARCA2, in cancer cell lines promoted their growth. These results showed that epigenetic and genetic alterations of chromatin remodelers are induced at an early stage of carcinogenesis and are frequently involved in the formation of a field defect.