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Objective. Endothelial cell-specific molecule 1 (ESM1) has been implicated as an oncogene in several types of cancer. However, the potential role of ESM1 in esophageal carcinogenesis (ESCA)/esophageal squamous cell carcinoma (ESCC) is still unclear. Methods. The expression, function, and survival data of ESM1 were observed using a bioinformatics approach. Subsequently, the expression level of ESM1 in surgical esophageal tumors and adjacent normal tissues was detected by qRT–PCR and immunofluorescence. We further revealed protein expression by immunohistochemistry (IHC), which is related to the prognosis of patients with ESCC using survival analysis. In vitro, knockdown of ESM1 in KYSE150 and KYSE510 cell lines, colony formation assays, wound healing assays, and Transwell assays were performed. Results. ESM1 is significantly elevated in 12 of 20 types of human cancer. ESM1 is highly expressed in tumor tissue compared with adjacent normal tissue and was identified as a hub gene in ESCA. Clinical outcome endpoints of overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) curves showed that patients whose ESM1 expression was high had a lower clinical survival rate. The ESM1 high-expression group has a certain correlation with clinical stage and grade. The IHC of ESM1 further demonstrated that the higher the expression was, the worse the N classification and pTNM stage in patients with ESCC, which had a distinctly poorer overall 5-year survival rate. Univariate analysis showed that age, N classification, pTNM stage, and ESM1 expression were all prognostic factors, although multivariate Cox regression analysis showed that only pTNM stage was an independent prognostic factor. In vitro, silencing ESM1 suppressed the proliferation, migration, and invasion of KYSE150 and KYSE510 cells. Conclusions. ESM1 is a hub gene in the initiation and progression of ESCA/ESCC that promotes the proliferation, migration, and invasion of esophageal cancer cells and may be a promising therapeutic target and prognostic indicator. [ABSTRACT FROM AUTHOR]

GINS2 is overexpressed in several cancers, but little is known about its role in osteosarcoma (OS). A series of in vivo and in vitro experiments were conducted to explore the role of GINS2 in OS. In this study, we demonstrated that GINS2 was found to be highly expressed in OS tissues and cell lines, which was associated with poor outcomes in OS patients. GINS2 knockdown hindered the growth and induced apoptosis in OS cell lines in vitro. Furthermore, GINS2 knockdown effectively inhibited the growth of a xenograft tumor in vivo. By using an Affymetrix gene chip and intelligent pathway analysis, it was demonstrated that the GINS2 knockdown could reduce the expression of several targeted genes and reduce the activity of the MYC signaling pathway. Mechanically, LC-MS, CoIP, and rescue experiments revealed that GINS2 promoted tumor progression through the STAT3/MYC axis in the OS. Moreover, GINS2 was associated with tumor immunity and may be a potential immunotherapeutic target for OS. [ABSTRACT FROM AUTHOR]

Vitamin D supplementation is regarded as a novel approach to treat Alzheimer's disease, but the underlying mechanism remains elusive. The cytokine IL-34 provides strong neuroprotective and survival signals in brain injury and neurode-generation and could be an immunological mediator for the vitamin D-induced protection. The aim of this study was to investigate whether human IL-34 is up-regulated in neuronal cells by the hormonally active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1α,25(OH)[sub 2]D[sub 3]]. We found that IL-34 was detectable in a variety of cell lines and its expression was strongly induced in SH-SY5Y neural cells in a dose- and time-dependent manner by 1α,25(OH)[sub 2]D[sub 3] through the vitamin D receptor (VDR). Furthermore, we identified the core promoter of IL-34 gene and a VDR binding site (CGCCCT) that was required for 1α,25(OH)[sub 2]D[sub 3]-induced IL-34 expression. These findings suggest that the induction of IL-34 expression by 1α,25(OH)[sub 2]D[sub 3] may constitute a mechanism that explains the protective function of vitamin D in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The overexpression of ATP-binding cassette (ABC) transporters is a common cause of multidrug resistance (MDR) in cancers. The intracellular drug concentration of cancer cells can be decreased relative to their normal cell counterparts due to increased expression of ABC transporters acting as efflux pumps of anticancer drugs. Over the past decades, antimicrobial peptides have been investigated as a new generation of anticancer drugs and some of them were reported to have interactions with ABC transporters. In this article, we investigated several novel antimicrobial peptides to see if they could sensitize ABCB1-overexpressing cells to the anticancer drugs paclitaxel and doxorubicin, which are transported by ABCB1. It was found that peptide XH-14C increased the intracellular accumulation of ABCB1 substrate paclitaxel, which demonstrated that XH-14C could reverse ABCB1-mediated MDR. Furthermore, XH-14C could stimulate the ATPase activity of ABCB1 and the molecular dynamic simulation revealed a stable binding pose of XH-14C-ABCB1 complex. There was no change on the expression level or the location of ABCB1 transporter with the treatment of XH-14C. Our results suggest that XH-14C in combination with conventional anticancer agents could be used as a novel strategy for cancer treatment. [ABSTRACT FROM AUTHOR]