Abstact: SOX2 is a transcription factor that contributes to transcription modification and cancer, but the mechanism by which SOX2 regulates nasopharyngeal carcinoma cell proliferation is not well understood. Here, we identify a SOX2 signaling pathway that facilitates nasopharyngeal carcinoma, where it is upregulated. SOX2 expression was associated with nasopharyngeal carcinoma patient survival. SOX2 knockdown inhibited cell proliferation, colony formation, and tumorigenesis in an subcutaneous mouse xenograft model system. Six hundred and ninety-nine candidate SOX2 downstream dysregulated genes were identified in nasopharyngeal carcinoma cells through cDNA microarray analysis. SOX2 recruited the nuclear transcription factor KLF4 to bind to the PIK3CA promoter upregulate PIK3CA expression, acting to enhance PI3K/AKT signaling and tumorigenesis by upregulating PIK3CA expression. Besides, overexpressing activated AKT or PIK3CA rescued the growth inhibition of cells due to SOX2 knockdown. Together, our study suggest that SOX2 exhibits oncogenic properties and may be a reliable molecular biomarker in nasopharyngeal carcinoma. Targeting SOX2 might be a promising treatment strategy for nasopharyngeal carcinoma treatment.

Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely. In current study, 11 DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. Four hundred and eighty two predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top 20 lncRNAs of BC were significantly identified. LINC00662 and LINC00963 expression were significantly associated with patients' overall survival (OS). Then, nine potential upstream transcription factors were identified in motifs of DE-miRNAs. Three hundred and twenty target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the topest connectivity scores. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. RAB7A and ARRB1 expression were significantly related with BC patients' OS.

The FK506-binding protein (FKBP) family plays a key role in a variety of tumors and is involved in the regulation of important signaling pathways including AKT, NF-κB and p53, which affects cell proliferation, migration, and multiple cell death modes. Here, we summarize the findings that different FKBP family members exhibit dual functions of promoting or inhibiting tumorigenesis in different types of tumors. The expression levels of FKBP family members are closely related to the prognosis of patients, thus might be used as potential diagnostic and prognostic biomarkers. In the future, it is necessary to combine single-cell sequencing to resolve the spatial distribution of FKBP isoforms, develop clinical validation to promote the translation from molecular mechanism to precision therapy.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Min Fang1, *, Tao Song1, *, Xiaodong Liang1, Shiliang Lv1, Jianbo Li2, Hong’en Xu1, Limin Luo1, Yongshi Jia1 1Department of Radiation Oncology, Zhejiang Provincial People’s Hospital, Hangzhou 310000, Zhejiang, P. R. China 2Department of Radiation Oncology, Ningbo Mingzhou Hospital, Ningbo 315000, Zhejiang, P. R. China *These authors contributed equally to this work Correspondence to: Limin Luo, email: luoliminflk@163.com Yongshi Jia, email: jyssrmyy@163.com Keywords: definitive concourrent chemoradiotherapy, esophageal squamous cell carcinoma, S-1, cisplatin, paclitaxel Received: June 20, 2016 Accepted: March 03, 2017 Published: March 14, 2017 ABSTRACT This study compared the efficiency and safety of definitive concurrent chemoradiotherapy (CCRT) using Paclitaxel plus Cisplatin (TP) versus S-1 plus Cisplatin (CS) in unresectable locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2009 and December 2013, 203 LAESCC patients were retrospectively reviewed. We performed a propensity score matching analysis; 41 patients treated with the CS regimen were matched 1:1 to patients who received the TP regimen. Patient- and disease-related characteristics were well-balanced between the two groups. The CS group showed significantly better treatment compliance (90.2% vs. 70.7%, P = 0.026) and less hospital stay (48 days vs 49 days, P = 0.025) over the TP group during the CCRT course. The complete response rate was comparable between the two groups (51.2% vs. 48.8%, P = 0.825). The 1- and 3-year overall survival (OS) rates in the TP group were 63.4% and 32.4% compared to 62.8% and 32.1% in the CS group, respectively (P = 0.796). The 1- and 3-year progression-free survival (PFS) rates in the TP group were 51.2% and 24.9%, compared to 53.6% and 18.9% in the CS group, respectively (P = 0.630). The incidence of severe and total neutropenia in the TP group was significantly higher compared to the CS group (P = 0.011 and 0.046, respectively). Multivariate analysis revealed that T stage and the complete response rate were strong prognostic factors associated with OS and PFS. In conclusion, both treatment regimens yielded satisfactory survival outcomes, but the CS regimen could significantly improve treatment compliance, reduce hematological toxicities and lengths of hospital stay. Future prospective studies in large cohorts are highly warranted to confirm the findings in our report.

TMEM173 is a pattern recognition receptor detecting cytoplasmic nucleic acids and transmits cGAS related signals that activate host innate immune responses. It has also been found to be involved in tumor immunity and tumorigenesis. In this study, we first identified that the FKBP4/NR3C1 axis was a novel negative regulator of TMEM173 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at the transcriptional level of TMEM173, because it could suppress the promoter activity of TMEM173, thereby affecting TMEM173 at mRNA and protein levels. Past studies, our bioinformatics analysis, and in vitro experiments further implied that FKBP4 regulated TMEM173 via regulating nuclear translocation of NR3C1. We then demonstrated that the FKBP4/NR3C1/TMEM173 signaling pathway could regulate autophagy and proliferation of BC cells as well as dendritic cell (DC) abundance through exosome release. Our study found an unprecedented strategy used by BC to escape from TMEM173 mediated tumor suppression. Identification of the FKBP4/NR3C1 axis as a novel TMEM173 regulator would provide insights for novel anti-tumor strategy against BC among tumor microenvironment.