Hepatic MCPIP1 protein levels are reduced in NAFLD patients and are predominantly expressed in cholangiocytes and liver endothelium.

Background And Aims: NAFLD is characterized by the excessive accumulation of fat in hepatocytes. NAFLD can range from simple steatosis to the aggressive form called NASH, which is characterized by both fatty liver and liver inflammation. Without proper treatment, NAFLD may further progress to life-threatening complications, such as fibrosis, cirrhosis, or liver failure.

Resistance to tyrosine kinase inhibitors promotes renal cancer progression through MCPIP1 tumor-suppressor downregulation and c-Met activation.

Tyrosine kinase inhibitors (TKIs) are the most commonly used targeted therapeutics in clear-cell renal cell carcinoma (ccRCC); however, drug resistance limits their utility and can lead to tumor "flare-up" and progression. In this study, we show that RCC resistance to sunitinib and sorafenib involves different mechanisms and leads to increased malignancy. Sunitinib decreased tumor growth and cell motility along with increased E-cadherin expression and secretion of the proangiogenic cytokines IL6 and IL8, which activated senescence in ccRCC cells and led to VE-cadherin phosphorylation, enhancing tumor angiogenesis.

MCPIP1 regulates focal adhesion kinase and Rho GTPase-dependent migration in clear cell renal cell carcinoma.

Metastasis is responsible for as many as 90% of cancer-associated deaths in patients. The metastatic process is a result of tumor cell migration and invasion associated with morphological changes and increased expression of several genes involved in cell migration. We have already shown that monocyte chemotactic protein-1-induced protein-1 (MCPIP1), a negative regulator of inflammatory processes, influences cell morphology, prevents the epithelial to mesenchymal transition program, and regulates metastasis in clear cell renal cell carcinoma (ccRCC).

MCPIP1 inhibits Wnt/β-catenin signaling pathway activity and modulates epithelial-mesenchymal transition during clear cell renal cell carcinoma progression by targeting miRNAs.

Epithelial-mesenchymal transition (EMT) refers to the acquisition of mesenchymal properties in cells participating in tumor progression. One hallmark of EMT is the increased level of active β-catenin, which can trigger the transcription of Wnt-specific genes responsible for the control of cell fate. We investigated how Monocyte Chemotactic Protein-1-Induced Protein-1 (MCPIP1), a negative regulator of inflammatory processes, affects EMT in a clear cell renal cell carcinoma (ccRCC) cell line, patient tumor tissues and a xenotransplant model.

Fatty Acids and a High-Fat Diet Induce Epithelial-Mesenchymal Transition by Activating TGFβ and β-Catenin in Liver Cells.

Nonalcoholic fatty liver disease is defined as the accumulation of excessive fat in the liver in the absence of excessive alcohol consumption or any secondary cause. Although the disease generally remains asymptomatic, chronic liver inflammation leads to fibrosis, liver cirrhosis, and even to the development of hepatocellular carcinoma (HCC). Fibrosis results from epithelial-mesenchymal transition (EMT), which leads to dedifferentiation of epithelial cells into cells with a mesenchymal-like phenotype.

Deletion of Mcpip1 in Mcpip1Alb mice recapitulates the phenotype of human primary biliary cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by progressive destruction of the intrahepatic bile ducts. The immunopathology of PBC involves excessive inflammation; therefore, negative regulators of inflammatory response, such as Monocyte Chemoattractant Protein-1-Induced Protein-1 (MCPIP1) may play important roles in the development of PBC. The aim of this work was to verify whether Mcpip1 expression protects against development of PBC.

The anti-inflammatory protein MCPIP1 inhibits the development of ccRCC by maintaining high levels of tumour suppressors.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer. It is highly vascularized and largely resistant to traditional chemo- and radiotherapy. Decreases in tumour suppressors and low levels of the anti-inflammatory Monocyte Chemoattractant Protein-Induced Protein 1 (MCPIP1) play important roles in the development and progression of ccRCC.

New therapeutic strategies in nonalcoholic fatty liver disease: a focus on promising drugs for nonalcoholic steatohepatitis.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Globally, it is currently the most common liver disease and is estimated to affect up to 25% of the population. In the first stage, NAFLD is characterized by simple hepatic steatosis (NAFL, nonalcoholic fatty liver) that might progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular carcinoma.

Activity of MCPIP1 RNase in tumor associated processes.

The monocyte chemoattractant protein-induced protein (MCPIP) family consists of 4 members (MCPIP1-4) encoded by the ZC3h12A-D genes, which are located at different loci. The common features of MCPIP proteins are the zinc finger domain, consisting of three cysteines and one histidine (CCCH), and the N-terminal domain of the PilT protein (PilT-N-terminal domain (PIN domain)). All family members act as endonucleases controlling the half-life of mRNA and microRNA (miRNA).

C-Met as a Key Factor Responsible for Sustaining Undifferentiated Phenotype and Therapy Resistance in Renal Carcinomas.

C-Met tyrosine kinase receptor plays an important role under normal and pathological conditions. In tumor cells' overexpression or incorrect activation of c-Met, this leads to stimulation of proliferation, survival and increase of motile activity. This receptor is also described as a marker of cancer initiating cells.

RNA sequencing reveals widespread transcriptome changes in a renal carcinoma cell line.

We used RNA sequencing (RNA-Seq) technology to investigate changes in the transcriptome profile in the Caki-1 clear cell renal cell carcinoma (ccRCC) cells, which overexpress monocyte chemoattractant protein-induced protein 1 (MCPIP1). RNA-Seq data showed changes in 11.6% and 41.

MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities.

MCPIP1 contributes to clear cell renal cell carcinomas development.

Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues. Using Caki-1 cells as a model, we analyzed the role of MCPIP1 in cancer development.

The Met tyrosine kinase receptor as a therapeutic target and a potential cancer stem cell factor responsible for therapy resistance (Review).

The MET tyrosine kinase receptor plays an important role during tumor development and progression being responsible for proliferation, morphogenetic transformation, cell motility and invasiveness. High expression of the MET receptor has been shown to correlate with increased tumor growth and metastasis, poor prognosis and resistance to radiotherapy. Moreover, MET expression and activation has been shown to be associated with therapy resistance.

Constitutive activation of MET signaling impairs myogenic differentiation of rhabdomyosarcoma and promotes its development and progression.

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma, which may originate from impaired differentiation of mesenchymal stem cells (MSC). Expression of MET receptor is elevated in alveolar RMS subtype (ARMS) which is associated with worse prognosis, compared to embryonal RMS (ERMS). Forced differentiation of ARMS cells diminishes MET level and, as shown previously, MET silencing induces differentiation of ARMS.

MET receptor is a potential therapeutic target in high grade cervical cancer.

Cervical cancer is one of the leading causes of death among women suffering from tumors. Current treatment options are insufficient. Here, we investigated the MET receptor as a potential molecular target in advanced cervical cancer.

Downregulation of the CXCR4 receptor inhibits cervical carcinoma metastatic behavior in vitro and in vivo.

Cervical carcinoma is frequently diagnosed among women, particularly in low and middle income countries. In this study, we investigated the role of the SDF-1/CXCR4 axis during cervical carcinoma growth and progression in vitro and in vivo. Downregulation of CXCR4 receptor using an RNA interference system led to almost complete inhibition of the receptor expression, activation and function.

Multifunctional protein APPL2 contributes to survival of human glioma cells.

Some endocytic proteins have recently been shown to play a role in tumorigenesis. In this study, we demonstrate that APPL2, an adapter protein with known endocytic functions, is upregulated in 40% cases of glioblastoma multiforme, the most common and aggressive cancer of the central nervous system. The silencing of APPL2 expression by small interfering RNAs (siRNAs) in glioma cells markedly reduces cell survival under conditions of low growth factor availability and enhances apoptosis (measured by executor caspase activity).

17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion.

Glioblastoma multiforme (GBM) is the most frequent and the most malignant human brain tumor. The expression of receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF) is strongly increased in GBM, where they promote tumor proliferation, cell survival, migration, invasion and angiogenesis. We used geldanamycins (GAs) (inhibitors of HSP90) in order to block glioblastoma growth and HGF-dependent cell migration and invasion.

Fenofibrate attenuates contact-stimulated cell motility and gap junctional coupling in DU-145 human prostate cancer cell populations.

In the present study, we investigated the effects of fenofibrate on the invasive potential of DU-145 human prostate cancer cells in the context of gap junctional intercellular coupling and the formation of reactive oxygen species. Time-lapse analyses of cell motility, accompanied by tests of cell viability, membrane microviscosity, reactive oxygen species accumulation and the function of gap junctional protein connexin 43 were performed in monolayer cultures of DU-145 cells following fenofibrate administration. Fenofibrate inhibited the motility of DU-145 cells and attenuated gap junctional intercellular coupling in a manner independent of its effects on cell viability, PPARα activation and cell membrane micro-viscosity.

Differential expression of Snail1 transcription factor and Snail1-related genes in alveolar and embryonal rhabdomyosarcoma subtypes.

Rhabdomyosarcoma (RMS) represents the most common sarcoma of soft tissue among children. Two main RMS subtypes are alveolar (ARMS) and embryonal (ERMS). The major goal of this study was to find differentially expressed genes between RMS subtypes that could explain higher metastatic potential in ARMS and would be useful for the differential diagnosis.

Genetically modified adipose tissue-derived mesenchymal stem cells overexpressing CXCR4 display increased motility, invasiveness, and homing to bone marrow of NOD/SCID mice.

Objective: This study evaluates usefulness of CXCR4 overexpression via retroviral transduction in adipose tissue-derived mesenchymal stem cells (AT-MSCs) as a strategy to increase their migration and engraftment ability.

Materials And Methods: AT-MSCs were isolated from lipoaspirates from human healthy donors with liberase 3. Cells were transduced with retroviral vector carrying either CXCR4 or green fluorescent protein (GFP) complementary DNA, and neo-resistant colonies were selected and used in experiments.

Role of I-TAC-binding receptors CXCR3 and CXCR7 in proliferation, activation of intracellular signaling pathways and migration of various tumor cell lines.

Chemokines and its receptors stimulate tumor growth, migration and invasion. In this study we evaluated the expression and function of CXCR3 and CXCR7 receptors in cervical carcinoma, rhabdomyosarcoma and glioblastoma cell lines. We found that both receptors were expressed at different degree by tumor cells.

Inhibition of rhabdomyosarcoma's metastatic behavior through downregulation of MET receptor signaling.

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma usually diagnosed in children. In advanced and metastatic stages the prognosis is often poor. RMS cell lines were used for evaluation of the role of MET receptor inhibition on chemotaxis and invasion.

Topographical control of prostate cancer cell migration.

Tumour cells can efficiently respond to numerous factors affecting their motility. However, the role of substrata topography in the regulation of cancer cell motility has been quantitatively studied in only a few cases. We demonstrated that human (DU-145) and rat (MAT-LyLu and AT-2) prostate cancer cells are efficiently contact guided by underlying normal cells when invading surrounding tissues and forming metastases.