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Purpose: Tumor initiating cells (TICs) or cancer stem cells (CSCs) are considered to be the main culprit of hepatocellular carcinoma (HCC) initiation and progression, nevertheless the mechanism by which tumor microenvironment maintains the HCC ‘stemness’ is not fully understood. This study aims to investigate the effect of regulatory T cells (Tregs) on the TICs characteristics of HCC. Methods: Immunocytochemistry, flow cytometry, real-time PCR, western blot, in vitro sphere-formation, and in vivo tumorigenesis assay were used to detect HCC ‘stemness’. Additionally, after forced expression or inhibition of FoxP3, β-catenin expression and HCC ‘stemness’ were investigated. Results: Tregs enhanced the ‘stemness’ of HCC cells by upregulating TIC-related markers CD133, Oct3/4, Sox2, c-Myc, Klf4, Nanog, CD13, EpCAM, and inducting epithelial to mesenchymal transition (EMT), increasing TICs ratio, as well as promoting tumorigenic ability. Moreover, β-catenin and c-Myc were upregulated in HCC cells after co-cultured with Tregs. HCC ‘stemness’ was inhibited after treatment with Wnt/β-catenin pathway inhibitor. Furthermore, forced expression of FoxP3 resulted in increased GSK3β, decreased β-catenin and TIC ratio in HCC. In contrast, FoxP3 interference reduced GSK3β, enhanced β-catenin and TIC ratio of HCC. Conclusion: This study, for the first time, demonstrated that Tregs increased the population of TICs in HCC by inhibiting FoxP3 as well as promoting β-catenin expression. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the most prevalent and deadliest cancer worldwide. The present study aims to determine the prognosis value of low expression long non-coding RNAs (lncRNAs) in LUAD. Methods: RNA-seq data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Dysregulated genes between LUAD and paracancerous tissue were screened by GeneSpringGX. Prognostic lncRNAs which were low expressed in LUAD were filtrated by Ualcan, then further verified through the TCGA database. The association between clinicopathological features and the expression level of these lncRNAs was tested by chi-square test. Cox regression analysis was performed to test independent prognosis risk factors. Diagnostic efficiency was predicted by receiver operating characteristic (ROC) analysis. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore potential functions of these prognostic signatures. Results: Nine prognostic lncRNAs (LINC00092, LINC00908, WWC2-AS2, RPL13AP17, CHIAP2, SFTA1P, SIGLEC17P, CYP2B7P1, CYP4Z2P) were screened out through Ualcan and further verified by TCGA. Among them, six lncRNAs (RPL13AP17, CHIAP2, SFTA1P, SIGLEC17P, CYP2B7P1, CYP4Z2P) were pseudogene transcripts. Multivariate Cox regression analysis showed that three lnRNAs (LINC00908, WWC2-AS2 CYP2B7P) were independent prognostic risk factors for OS and two lncRNAs (WWC2-AS2, SIGLEC17P) were independent prognostic risk factors for RFS in LUAD patients. Meanwhile, they showed powerful diagnostic value by ROC curve analysis. GO analysis revealed correlation genes of prognostic signatures were mainly enriched in plasma membrane, plasma membrane part, purine nucleotide binding, cytoskeleton and ribonucleotide binding and KEGG pathway analysis showed mainly enriched in cell adhesion molecules. Conclusions: The results illuminated that four lncRNAs (LINC00908, WWC2-AS2, CYP2B7P, SIGLEC17P) may be a powerful diagnostic and prognostic assessment tool for human LUAD. [ABSTRACT FROM AUTHOR]

The aberrant expression of retinoic acid receptor‑α (RARα) has been reported in various types of cancer. However, its association with the prognosis and development of laryngeal squamous cell carcinoma (LSCC) has not yet been determined. Therefore, the present study aimed to examine the expression and function of RARα in patients with LSCC. The expression of RARα in LSCC tissues was investigated using immunostaining. An MTT assay and flow cytometry analysis were also performed to investigate the function of RARα in the proliferation and cell cycle of LSCC cells. The expression of RARα was significantly elevated in LSCC tissues compared with adjacent noncancerous tissues (78.1 vs. 6.3%, P<0.05). The overexpression of RARα was associated with poorly differentiated features of LSCC (P<0.05). Furthermore, the downregulation of RARα inhibited the proliferation of LSCC cells, and arrested the cell cycle at the G1 phase via upregulation of cyclin dependent kinase inhibitor 1A, which may be associated with inhibition of the protein kinase B signaling pathway. Therefore, the overexpression of RARα may contribute to the development of LSCC through the regulation of the cell cycle. The results of the present study provide evidence that RARα serves an important function in LSCC development and may be a potential therapeutic target or prognostic predictor for LSCC. [ABSTRACT FROM AUTHOR]

Abstract Purpose  Dofetilide (DOF), a novel Class III antiarrhythmic drug, prolongs the action potential duration (APD) and shows a positive inotropic effect in guinea pig papillary muscle. The present experiments were designed to study the positive inotropic effect of DOF on rat ventricle and explore its possible mechanism(s). Methods  Hearts from male Wistar rats (260–320 g) were divided into five groups and perfused in Langendorff mode. Ventricular myocytes were enzymatically isolated from male Wistar rats. Whole-cell voltage-clamping technique was used to test the Na+–Ca2+ exchange (NCE) current (I NCX); Calcium transients and cell shortening provoked by field stimulation or using calcium current command waveform were observed synchronously with an ionic imaging system. Results  DOF (0.03–1.0 μM) increased left ventricular function in isolated rat hearts in a concentration-dependent manner. DOF (0.03–1.0 μM) also concentration-dependently increased both inward and outward I NCX in isolated rat ventricular cells. The EC50 values of DOF were 0.149 μM for the inward I NCX and 0.249 μM for outward I NCX, respectively. DOF 0.2 μM significantly enhanced Ca2+ transient and cell shortening in single rat ventricular myocytes driven by field electric stimulation. When the patch clamp system was connected to the ionic imaging system, Ca2+ current (I Ca), Ca2+ transient and cell shortening amplitude in a same cell were recorded synchronously. Application of DOF 0.2 μM had no effect on I Ca, but significantly increased Ca2+ transient and cell shortening. NCX inhibitor KB-R7943 0.6 μM significantly depressed the effects of DOF on Ca2+ transient and cell shortening. Conclusions  We conclude that DOF enhanced contractility of rat ventricular myocytes. The enhancement of NCE may be involved in the positive inotropic action of DOF. [ABSTRACT FROM AUTHOR]