Anti-PTTG1 (aa 1-100) polyclonal antibody

Non-alcoholic steatohepatitis (NASH) is a type of nonalcoholic fatty liver disease and has become a major risk factor for hepatocellular carcinoma (HCC). However, the underlying pathophysiological mechanisms are still elusive. Here, we identify hyaluronan-mediated motility receptor (HMMR) as a critical gene associated with NASH/HCC by combination of bioinformatic analysis and functional experiments. Analysis of differentially expressed genes (DEGs) between normal controls and NASH/HCC identified 5 hub genes (HMMR, UBE2T, TYMS, PTTG1 and GINS2). Based on the common DEGs, analyses of univariate and multivariate Cox regression and the area under the curve (AUC) value of the receiver operating characteristic (ROC) indicate that HMMR is the most significant gene associated with NASH/HCC among five hub genes. Oleate acid (OA), one of fatty acids that induce cellular adipogenesis, stimulates HMMR expression via CCAAT/enhancer-binding protein alpha (CEBP alpha). CEBP alpha increases the expression of HMMR through binding to its promoter. HMMR promotes HCC cell proliferation in vitro via activation of G1/S and G2/M checkpoint transitions, concomitant with a marked increase of the positive cell cycle regulators, including cyclin D1, cyclin E, and cyclin B1. Knockdown of HMMR suppresses HCC tumor growth in nude mice. Our study identifies an important role of HMMR in NASH/HCC, and suggests that HMMR may be a useful target for therapy and prognostic prediction of NASH/HCC patients.

This study aimed to construct a long noncoding RNA (lncRNA)-based prognostic signature to improve the survival prediction for endometrial cancer (EC) patients and guide individualized treatments. mRNA and miRNA sequencing and clinical data of 526 patients with EC (randomized to training or validation set, n = 263) were collected from The Cancer Genome Atlas database. Differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed miRNAs (DEMs) were identified between 263 EC samples and 33 normal controls. Univariate and multivariate Cox regression analyses identified five DELs (LINC00475, LINC01352, MIR503HG, KCNMB2-AS1, and LINC01143) that were overall survival related. The Kaplan-Meier curve showed that the risk score model established by these five DELs can significantly distinguish the survival ratio of patients at high risk from those at low risk. The receiver operating characteristic curve indicated that this risk score exhibited good survival prediction performance, with the area under the curve of 0.978. In addition, this risk score was independent of other clinical factors. Stratification analysis based on two independent prognostic clinical factors (histologic grade and recurrence status) demonstrated that the high-risk score was still a poor prognostic factor for patients with histologic grade 3, recurrence or nonrecurrence status. In nomogram model, the risk score was one of the main contributions to survival rates, and its Harrell's concordance index was higher than the other two independent clinical factors, although all lower than the combined. Furthermore, mechanism analyses showed that these lncRNAs functioned by coexpressing with DEGs (i.e., LINC00475-PTGDR, LINC01352/MIR503HG-BACH2, KCNMB2-AS1-PCSK9, LINC01143-NUF2/PTTG1) or as a competing endogenous RNA of DEMs to regulate DEGs (LINC00475-miR-4728-PTGDR, MIR503HG-miR-3170-BACH2). In conclusion, our novel risk score system may be a promising prognostic biomarker to guide personalized treatment for EC patients and it can add prognostic value for current clinical system.