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lrrca, cells, pubmed, cell, expression, cancer, article, nugc, central, sirna, fig, google, scholar, mkn, pmid, analysis, knockdown, supplementary, results, pathway, cas, ihc, invasion, signaling, patients, showed, gastric, proliferation, genes, jnk, control, pmcid, pmcpmc, apoptosis, intracellular, cycle, usa, human, migration, japan, shiozaki, staining, transfection, protein, chloride, obtained, vrac, assay, significantly, lowchloride,

Topics {✒️}

pt-based anti-cancer drugs mouse monoclonal anti-beta-actin rabbit polyclonal anti-sapk/jnk real-time pcr system real-time rt-pcr volume-regulated anion channel top-ranked canonical pathways semi-quantitatively graded based full size image sulfate–polyacrylamide gel electrophoresis suppressing pi3k/akt activation chloride-sensitive fluorescence probe tmr-conjugated halotag ligand avidin-biotinylated peroxidase complex mouse monoclonal anti-p53 anti-phospho-sapk/jun housekeeping gene beta-actin low-chloride stimulation suppressed diff-quick staining reagents low-chloride stimulation assay anti-rabbit secondary antibodies avidin/biotin blocking kit annexin v-fitc kit pubmed central pmcid low-chloride stimulation experiment stress-activated protein kinases low-chloride medium supplemented fluorescence-activated cell sorting intracellular chloride regulates g0/g1 arrest k-cl cotransporter kcc3 intracellular chloride concentration lrrc8a-depleted nugc4 cells gastric cancer cells lrrc8a-regulated cell proliferation privacy choices/manage cookies article kurashima quantitative rt-pcr low-chloride stimulation cell cycle progression leucine-rich repeat primary tissue samples 7076s/anti-rabbit top-ranked diseases cancerous gastric epithelia intracellular ion environment colon cancer patients constant cell volume g0/g1 phase swelling-induced release

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         headline:LRRC8A influences the growth of gastric cancer cells via the p53 signaling pathway
         description:Leucin-rich repeat containing protein A (LRRC8A), a component of the volume-regulated anion channel (VRAC), is activated by cell swelling and mediates regulatory volume decrease. We previously reported the expression of and important roles for several ion transporters in various gastrointestinal cancers, which have potential as novel targets for cancer treatment; however, the significance of LRRC8A in gastric cancer (GC) remains unclear. Knockdown experiments were performed by transfecting human GC cell lines with LRRC8A siRNA. Gene expression was then assessed using microarray analysis. Samples from 132 patients with GC were subjected to immunohistochemistry (IHC) for LRRC8A, and its relationships with clinicopathological factors and prognosis were examined. The knockdown of LRRC8A suppressed the proliferation and movement of cells and enhanced apoptosis. The results of the microarray analysis showed the up- or down-regulated expression of genes related to the p53 signaling pathway (JNK, p53, p21, Bcl-2, and FAS) in LRRC8A-knockdown cells. IHC revealed a correlation between the expression of LRRC8A and the pT status (p = 0.015), and multivariate analysis identified the strong expression of LRRC8A as an independent prognostic factor for 5-year survival in GC patients (p = 0.0231). The present results indicate that LRRC8A functions as a mediator of and/or biomarker for GC.
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      description:Leucin-rich repeat containing protein A (LRRC8A), a component of the volume-regulated anion channel (VRAC), is activated by cell swelling and mediates regulatory volume decrease. We previously reported the expression of and important roles for several ion transporters in various gastrointestinal cancers, which have potential as novel targets for cancer treatment; however, the significance of LRRC8A in gastric cancer (GC) remains unclear. Knockdown experiments were performed by transfecting human GC cell lines with LRRC8A siRNA. Gene expression was then assessed using microarray analysis. Samples from 132 patients with GC were subjected to immunohistochemistry (IHC) for LRRC8A, and its relationships with clinicopathological factors and prognosis were examined. The knockdown of LRRC8A suppressed the proliferation and movement of cells and enhanced apoptosis. The results of the microarray analysis showed the up- or down-regulated expression of genes related to the p53 signaling pathway (JNK, p53, p21, Bcl-2, and FAS) in LRRC8A-knockdown cells. IHC revealed a correlation between the expression of LRRC8A and the pT status (p = 0.015), and multivariate analysis identified the strong expression of LRRC8A as an independent prognostic factor for 5-year survival in GC patients (p = 0.0231). The present results indicate that LRRC8A functions as a mediator of and/or biomarker for GC.
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      name:Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
      name:Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
      name:Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
      name:Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
      name:Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
      name:Department of Surgical Pathology, Kyoto City Hospital, Kyoto, Japan
      name:Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan
      name:Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan

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