Dysregulated JAK/STAT signaling has been implicated in the molecular pathogenesis of gastric cancer. However, downstream effectors of STAT signaling that facilitate gastric carcinogenesis remain to be explored. We previously identified the ortholog of human GRAMD1B in our genome-wide RNAi screen to identify novel components of the JAK/STAT signaling pathway in . Here, we examined the involvement of GRAMD1B in JAK/STAT-associated gastric carcinogenesis. We found that GRAMD1B expression is positively regulated by JAK/STAT signaling and GRAMD1B inhibition decreases STAT3 levels, suggesting the existence of a positive feedback loop. Consistently, GRAMD1B and JAK/STAT signaling acted synergistically to promote gastric cancer cell survival by upregulating the expression of the anti-apoptotic molecule Bcl-xL. Interestingly, our immunohistochemical analysis for GRAMD1B revealed a gradual loss of cytoplasmic staining but an increase in the nuclear accumulation of GRAMD1B, as gastric tissue becomes malignant. GRAMD1B expression levels were also found to be significantly associated with clinicopathological features of the gastric cancer patients, particularly the tumor grades and lymph node status. Moreover, GRAMD1B and pSTAT3 (Tyr705) showed a positive correlation in gastric tissues, thereby confirming the existence of a close link between these two signaling molecules . This new knowledge about JAK/STAT-GRAMD1B regulation deepens our understanding of JAK/STAT signaling in gastric carcinogenesis and provides a foundation for the development of novel biomarkers in gastric cancer.
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http://dx.doi.org/10.18632/oncotarget.23265 | DOI Listing |
Tuberculosis (Edinb)
December 2024
Shanxi Provincial Key Laboratory for Medical Molecular Cell Biology, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, and Institutes of Biomedical Sciences, Shanxi University, Taiyuan, 030006, China. Electronic address:
Background: Immune imbalance is crucial in tuberculosis pathogenesis and may be modulated by mesenchymal stem cells (MSCs). However, how MSCs regulate the host's response to Mycobacterium tuberculosis (Mtb) is unclear.
Methods: Human umbilical cord-derived MSCs were co-cultured with Mtb-infected THP-1 macrophages.
Mol Biol (Mosk)
December 2024
Faculty of Biology, Moscow State University, Moscow, 119234 Russia.
As a result of molecular domestication of the gag gene of errantiviruses, the Gagr gene was formed in the genome of Drosophila melanogaster. It has previously been shown that the Gagr gene is transcribed at the highest level in gut tissues relative to other tissues, and its transcription is most effectively induced in females in response to ammonium persulfate added to the nutrient medium. In the present work, the gut transcriptome of females with knockdown of the Gagr gene was studied in all tissues under standard conditions and under stress conditions caused by ammonium persulfate.
View Article and Find Full Text PDFCell Biol Toxicol
December 2024
Department of Hematology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China.
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid progenitor cells. Despite advancements in treatment, the prognosis for AML patients remains poor, highlighting the need for novel therapeutic targets. Protein Tyrosine Phosphatase Non-Receptor Type 6 (PTPN6), also known as SHP-1, is a critical regulator of hematopoietic cell signaling and has been implicated in various leukemias.
View Article and Find Full Text PDFBlood Res
December 2024
Department of Laboratory Hematology and Blood Bank, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Introduction: Despite advances in the treatment of acute myeloid leukemia (AML), refractory forms of this malignancy and relapse remain common. Therefore, development of novel, synergistic targeted therapies are needed urgently. Recently, mesenchymal stem cells (MSCs) have been shown to be effective in treating various diseases, with most of their therapeutic outcomes attributed to their exosomes.
View Article and Find Full Text PDFMol Neurobiol
December 2024
Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
The effective therapeutics for vascular dementia are still lacking. Here, we designed a novel derived peptide of erythropoietin-DEPO and evaluated its safety, erythropoiesis effect, and neuroprotective effects in mice of vascular dementia. For evaluating the safety and erythropoiesis, DEPO was injected into naive C57BL6 mice (n = 5) for 4-8 weeks, and venous blood was collected at 1, 2, and 4 weeks after DEPO treatment.
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