Hepatic TNFRSF12A promotes bile acid-induced hepatocyte pyroptosis through NFκB/Caspase-1/GSDMD signaling in cholestasis.

Tumor necrosis factor receptor superfamily member-12A (TNFRSF12A) plays a critical role in inflammation and cell death. It is expressed in multiple tissues yet extremely low in normal liver. To date, little is known about its role in cholestasis.

SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface.

Genetic polymorphisms are associated with the development of nonalcoholic fatty liver disease (NAFLD). Semaphorin7a (Sema7a) deficiency in mouse peritoneal macrophages reduces fatty acid (FA) oxidation. Here, we identified 17 individuals with SEMA7A heterozygous mutations in 470 patients with biopsy-proven NAFLD.

A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis.

Semaphorin 7A (SEMA7A) is a membrane-bound protein that involves axon growth and other biological processes. SEMA7A mutations are associated with vertebral fracture and Kallmann syndrome. Here, we report a case with a mutation in SEMA7A that displays familial cholestasis.

2,5-dimethyl celecoxib induces apoptosis and autophagy via activation of ROS/JNK axis in nasopharyngeal carcinoma cells.

2,5-dimethyl celecoxib (DMC), a close derivative of celecoxib, has also been reported to have anticancer effects. However, the effects and underlying molecular mechanisms of DMC with respect to nasopharyngeal carcinoma are still largely unknown. In this study, we present that DMC has displayed anticancer potency in nasopharyngeal carcinoma and .

Combination therapy of obeticholic acid and ursodeoxycholic acid in patients with primary biliary cholangitis who respond incompletely to ursodeoxycholic acid: a systematic review.

Background: Although the efficacy of ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) for primary biliary cholangitis (PBC) has been suggested by small trials, a meta-analysis to summarize the evidence has not yet been carried out. The aim of this study was to evaluate the clinical outcomes of the combination therapy of UDCA and OCA compared with UDCA monotherapy in patients with PBC.

Methods And Materials: We searched the PubMed, EMBASE, the web of science, and the Cochrane Library databases for English-language studies published before September 2018.

MiR-125b Increases Nasopharyngeal Carcinoma Radioresistance by Targeting A20/NF-κB Signaling Pathway.

Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA regulates this phenomenon. In this study, we investigated the function and mechanism of miR-125b in NPC radioresistance, one of upregulated miRNAs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-125b was frequently upregulated in the radioresistant NPCs, and its increment was significantly correlated with NPC radioresistance, and was an independent predictor for poor patient survival.

MiR-125b regulates proliferation and apoptosis of nasopharyngeal carcinoma by targeting A20/NF-κB signaling pathway.

MiR-125b is aberrantly expressed and has a role in the various types of tumors. However, the role and mechanism of miR-125b in nasopharyngeal carcinoma (NPC) are unclear. In this study, we investigated the role and mechanism of miR-125b in NPC.

Reduced RKIP enhances nasopharyngeal carcinoma radioresistance by increasing ERK and AKT activity.

Raf kinase inhibitory protein (RKIP) functions as a chemo-immunotherapeutic sensitizer of cancers, but regulation of RKIP on tumor radiosensitivity remains largely unexplored. In this study, we investigate the role and mechanism of RKIP in nasopharyngeal carcinoma (NPC) radioresistance. The results showed that RKIP was frequently downregulated in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and its reduction correlated with NPC radioresistance and poor patient survival, and was an independent prognostic factor.

Integrated analysis of the differential cellular and EBV miRNA expression profiles in microdissected nasopharyngeal carcinoma and non-cancerous nasopharyngeal tissues.

Nasopharyngeal carcinoma (NPC) is commonly diagnosed in southern Asia. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. Increasing evidence suggests that the dysregulation of miRNAs promotes NPC tumorigenesis.

MiR-23a sensitizes nasopharyngeal carcinoma to irradiation by targeting IL-8/Stat3 pathway.

Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA regulates this phenomenon. In this study, we investigated the function and mechanism of miR-23a in NPC radioresistance, one of downregulated miRNAs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-23a was frequently downregulated in the radioresistant NPC tissues, and its decrement correlated with NPC radioresistance and poor patient survival, and was an independent predictor for reduced patient survival.

MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT Signaling.

Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA (miR) regulates this phenomenon. In this study, we investigated the function and mechanism of miR-203 in NPC radioresistance, one of downregulated miRs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-203 was frequently downregulated in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and its decrement significantly correlated with NPC radioresistance and poor patient survival, and was an independent predictor for reduced patient survival.

Reduction of RKIP expression promotes nasopharyngeal carcinoma invasion and metastasis by activating Stat3 signaling.

The role and underlying mechanism of Raf kinase inhibitory protein (RKIP) in nasopharyngeal carcinoma (NPC) metastasis remain unclear. Here, we showed that RKIP was downregulated in the NPC with high metastatic potentials, and its decrement correlated with NPC metastasis and poor patient survival, and was an independent predictor for reduced overall survival. With a combination of loss-of-function and gain-of-function approaches, we observed that high expression of RKIP reduced invasion, metastasis and epithelial to mesenchymal transition (EMT) marker alternations of NPC cells.

The function and significance of SELENBP1 downregulation in human bronchial epithelial carcinogenic process.

Background: Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1) was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC) carcinogenesis.

Methods: iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process.

Identification of integrin β1 as a prognostic biomarker for human lung adenocarcinoma using 2D-LC-MS/MS combined with iTRAQ technology.

To discover novel lung adenocarcinoma (AdC) biomarkers, isobaric tags for relative and absolute quantitation (iTRAQ)-tagging combined with 2D-LC-MS/MS analysis was used to identify differentially expressed plasma membrane proteins in lung AdC and paired paraneoplastic normal lung tissues (PNLTs) adjacent to tumors. In this study, significant caveolin-1 downregulation and integrin β1 upregulation was observed in primary lung AdC vs. PNLT.

Annexin A1: a new biomarker for predicting nasopharyngeal carcinoma response to radiotherapy.

Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance remains a serious obstacle to successful treatment in many cases. Therefore, the biomarkers for predicting NPC response to radiotherapy are very important for targeted therapy and individualized radiotherapy of NPC. Accumulating evidences have shown that Annexin A1 was correlated with NPC radioresistance.

Identification of flotillin-1 as a novel biomarker for lymph node metastasis and prognosis of lung adenocarcinoma by quantitative plasma membrane proteome analysis.

To identify a novel lung adenocarcinoma (AdC) biomarker, iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed plasma membrane (PM) proteins in primary lung AdCs and paraneoplastic normal lung tissues (PNLTs). As a result, 36 differentially expressed membrane proteins were identified. Two differential PM proteins flotillin-1 and caveolin-1 were selectively validated by Western blotting.

Identification of heat shock protein 27 as a radioresistance-related protein in nasopharyngeal carcinoma cells.

Purpose: To identify the proteins involved in radioresistance in nasopharyngeal cancer (NPC) cells.

Methods: Sublethal ionizing radiation was applied to establish a radioresistant NPC cell line from its parental NPC cell line CNE1. Clonogenic survival assay, cell growth assay and flow cytometry analysis were used to examine the difference of radiosensitivity in the radioresistant CNE1 cells (CNE1-IR) and control CNE1 cells.

Identification of nm23-H1 as a metastatic suppressor and prognostic factor in nasopharyngeal carcinoma by proteomic analysis.

Objective: To identify proteins associated with nasopharyngeal carcinoma (NPC) metastasis, and provide scientific basis for the prevention and cure of NPC.

Methods: A two-dimensional gel electrophoresis and mass spectrometry were performed to screen for differential proteins between highly metastatic 5-8F and non-metastatic 6-10B NPC cell lines. Western blot was used to confirm the differential proteins.

Identification of candidate biomarkers for early detection of human lung squamous cell cancer by quantitative proteomics.

To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffin-embedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis.

Identification of GLIPR1 tumor suppressor as methylation-silenced gene in acute myeloid leukemia by microarray analysis.

Purpose: To identify methylation-silenced genes in acute myeloid leukemia (AML).

Methods: Microarray analyses were performed in AML cell line HL-60 cells exposed to the demethylating agent 5-aza-2dC. The methylation status and expression of glioma pathogenesis-related protein 1 (GLIPR1), one of highly induced genes by demethylation, were further detected in six hematopoietic malignancy cell lines and 260 bone marrow samples from leukemia patients and nonmalignant diseases as control, as well as pre-treated and post-treated bone marrow samples from 24 complete remission AML patients received chemotherapy using MS-PCR, bisulfite DNA sequencing, RT-PCR, and Western blotting.

Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics.

Background: The epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC) and is associated with pathogenesis of NPC. However, the downstream signaling proteins of EGFR in NPC have not yet been completely understood at the system level. The aim of this study was identify novel downstream proteins of EGFR signaling pathway in NPC cells.

Activation of EGFR promotes squamous carcinoma SCC10A cell migration and invasion via inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin.

EGFR is a potent stimulator of invasion and metastasis in head and neck squamous cell carcinomas (HNSCC). However, the mechanism by which EGFR may stimulate tumor cell invasion and metastasis still need to be elucidated. In this study, we showed that activation of EGFR by EGF in HNSCC cell line SCC10A enhanced cell migration and invasion, and induced loss of epitheloid phenotype in parallel with downregulation of E-cadherin and upregulation of N-cadherin and vimentin, indicating that EGFR promoted SCC10A cell migration and invasion possibly by an epithelial to mesenchymal transition (EMT)-like phenotype change.

Identification of the proteins related to p53-mediated radioresponse in nasopharyngeal carcinoma by proteomic analysis.

Radiotherapy is the primary treatment for nasopharyngeal cancer (NPC), and p53 is closely associated with the radiosensitivity of cancer, but the molecular mechanisms of p53-mediated radioresponse in NPC remains unclear. We previously established NPC CNE2sip53 cell line with p53 knockdown and paired control cell line CNE2/pSUPER, which provides a cell model system to investigate mechanisms of p53-mediated radioresponse in NPC. In this study, we first compared the radiosensitivity of CNE2sip53 and CNE2/pSUPER by a clonogenic survival assay, cell growth assay, and Hoechst 33258 staining and flow cytometry analysis of apoptotic cells.