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Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Extracellular Vesicles Promotes Hepatic Stellate Cell Activation, Liver Fibrosis and β-Catenin Signaling Pathway
Evidence shows that the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) is associated with activation of hepatic stellate cells (HSCs) and liver fibrosis in animal and in vitro studies. However, its roles in human liver fibrosis and the underlying mechanism in HSC activation are not yet defined. In our current study, the expression of Lnc-MALAT1 in the fibrotic liver tissues and in the plasma extracelllar vesicles (EVs) of liver fibrosis patients was detected by FISH and qRT-PCR. The results revealed that enhanced expression of Lnc-MALAT1 was co-localized with increased expression of ...
Source: Frontiers in Physiology - February 14, 2022 Category: Physiology Source Type: research

DCLK1 inhibition attenuates tumorigenesis and improves chemosensitivity in esophageal squamous cell carcinoma by inhibiting β-catenin/c-Myc signaling.
In this study, real-time PCR and western blot analysis confirmed significant upregulation of DCLK1 expression in human ESCC tissues and cell lines. CCK-8 assay showed that transfection with siRNA against DCLK1 (si-DCLK1) markedly inhibited cell proliferation and colony formation in the ESCC cell lines Eca109 and TE1. Transwell assay revealed that si-DCLK1 transfection inhibited the migratory and invasive capacities of Eca109 and TE1 cells. Moreover, si-DCLK1 increased the chemosensitivity of these cells to cisplatin, as indicated by inhibited cell viability and colony formation, and increased ROS and apoptosis in cisplatin...
Source: Pflugers Archiv : European Journal of Physiology - June 11, 2020 Category: Physiology Authors: Zhang L, Zhou S, Guo E, Chen X, Yang J, Li X Tags: Pflugers Arch Source Type: research

Yes-Associated Protein 1 Plays Major Roles in Pancreatic Stellate Cell Activation and Fibroinflammatory Responses
Conclusion: Our data suggest a central role for YAP in sustaining the activated phenotype and fibroinflammatory responses in PaSC. Moreover, our findings indicate that a complex crosstalk between YAP, TGFβ1, and PDGF pathways regulates PaSC activity and growth.
Source: Frontiers in Physiology - December 2, 2019 Category: Physiology Source Type: research

The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer.
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive cancer, with low survival rates and limited therapeutic options. Thus, the elucidation of signaling pathways involved in PDAC pathogenesis is essential to identify novel potential therapeutic gene targets. Here, we used a systems approach by integrating gene and microRNA profiling analyses together with CRISPR/Cas9 technology, to identify novel transcription factors involved in PDAC pathogenesis. FOXA2 transcription factor was found to be significantly down-regulated in PDAC relative to control pancreatic tissues. Functional experiments revealed...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 4, 2016 Category: Physiology Authors: Vorvis C, Hatziapostolou M, Mahurkar-Joshi S, Koutsioumpa M, Williams J, Donahue TR, Poultsides GA, Eibl G, Iliopoulos D Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

ANO1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC).
Abstract Pancreatic ductal adenocarcinoma (PDAC) has one of the worst survival rates of all cancers. ANO1 (TMEM16A) is a recently identified Ca(2+)-activated Cl(-) channel (CaCC) that is upregulated in several tumors. Although ANO1 was subject to extensive studies in the recent years, its pathophysiological function has only been poorly understood. The aim of the present study is to establish the significance of ANO1 in PDAC behavior and demarcate its roles in PDAC from those of the volume-regulated anion channel (VRAC). We performed qPCR and Western blot measurements on different PDAC cell lines (Panc-1, Mia PaCa...
Source: Pflugers Archiv : European Journal of Physiology - August 28, 2014 Category: Physiology Authors: Sauter DR, Novak I, Pedersen SF, Larsen EH, Hoffmann EK Tags: Pflugers Arch Source Type: research

B7-H4 downregulation induces mitochondrial dysfunction and enhances doxorubicin sensitivity via the cAMP/CREB/PGC1-α signaling pathway in HeLa cells.
Abstract B7-H4 is a B7 family coregulatory protein that inhibits T cell-mediated immunity. B7-H4 is overexpressed in various cancers; however, the functional role of B7-H4 in cancer metabolism is poorly understood. Because mitochondria play pivotal roles in development, proliferation, and death of cancer cells, we investigated molecular and functional alterations of mitochondria in B7-H4-depleted HeLa cells. In a human study, overexpression of B7-H4 was confirmed in the cervices of adenocarcinoma patients (n = 3) compared to noncancer patients (n = 3). In the cell line model, B7-H4 depletion was performed ...
Source: Pflugers Archiv : European Journal of Physiology - March 23, 2014 Category: Physiology Authors: Kim HK, Song IS, Lee SY, Jeong SH, Lee SR, Heo HJ, Thu VT, Kim N, Ko KS, Rhee BD, Jeong DH, Kim YN, Han J Tags: Pflugers Arch Source Type: research

Expression of bile acid receptor TGR5 in gastric adenocarcinoma.
In this study we determined the expression of TGR5 in gastric adenocarcinoma and examined the role of TGR5 in cell proliferation. Strong TGR5 staining was present in 12% of cases of intestinal metaplasia but in no cases of normal gastric epithelium (p<0.01). Moderate to strong TGR5 membranous and cytoplasmic staining was present in 52% of the intestinal but in only 25% of the diffuse subtype of adenocarcinomas (p<0.001). Kaplan-Meier univariate survival analysis revealed that moderate to strong TGR5 staining was associated with decreased patient survival (p<0.05). Treatment with taurodeoxycholic acid (TDCA, a bile...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 13, 2012 Category: Physiology Authors: Cao W, Tian W, Hong J, Li D, Tavares R, Noble L, Moss SF, Resnick MB Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research