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Purpose: Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC.Experimental Design: RNA sequencing (RNA-seq) was applied to look for interchromosome translocation in NPC. PCR, FISH, and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies. MTT assay, colony formation assay, sphere formation assay, co-immunoprecipitation, chromatin immunoprecipitation assay, and in vivo chemoresistance assay were applied to explore the function of RARS-MAD1L1 in NPC.Results: We demonstrated that RARS-MAD1L1 was present in 10.03% (35/349) primary NPC biopsies and 10.7% (9/84) in head and neck cancer (HNC) samples. RARS-MAD1L1 overexpression increased cell proliferation, colony formation, and tumorigenicity in vitro, and the silencing of endogenous RARS-MAD1L1 reduced cancer cell growth and colony formation in vitro In addition, RARS-MAD1L1 increased the side population (SP) ratio and induced chemo- and radioresistance. Furthermore RARS-MAD1L1 interacted with AIMP2, which resulted in activation of FUBP1/c-Myc pathway. The silencing of FUBP1 or the administration of a c-Myc inhibitor abrogated the cancer stem cell (CSC)-like characteristics induced by RARS-MAD1L1. The expression of c-Myc and ABCG2 was higher in RARS-MAD1L1-positive HNC samples than in negative samples.Conclusions: Our findings indicate that RARS-MAD1L1 might contribute to tumorigenesis, CSC-like properties, and therapeutic resistance, at least in part, through the FUBP1/c-Myc axis, implying that RARS-MAD1L1 might serve as an attractive target for therapeutic intervention for NPC. Clin Cancer Res; 24(3); 659-73. ©2017 AACR.

Background: Tumor‐associated immune factors are heterogeneous and play an important role in determining outcome in cancer patients. In this study, the expression levels of immune factors in tumor tissue‐conditioned media from lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) were analyzed. Methods: LUAD and LUSC tissue specimens were collected immediately after surgery for antibody array analysis and real‐time quantitative PCR. Results: Higher levels of chemokines MCP1/CCL2 (21.11‐fold increase) and MIP‐1β/CCL4 (19.33‐fold increase) were identified in LUAD than in LUSC. Western blot and quantitative real‐time PCR analyses showed higher co‐expression of CCL2 and CCL4 in LUAD tissues compared to LUSC (P < 0.0001). Immunofluorescent co‐staining showed a high percentage of CCL2+/CD68+ and CCL4+/CD68+ tumor‐associated macrophages in LUAD compared to LUSC tissues, which might be responsible for the higher expression of CCL2 and CCL4 in LUAD samples. Kaplan–Meier curves showed that CCL2 overexpression in patients with LUSC was associated with beneficial overall survival (OS; P = 0.048) and progression‐free survival (PFS; P = 0.012); however, LUAD patients with higher CCL2 expression had unfavorable OS (P = 6.7e−08) and PFS (P = 0.00098). Similarly, CCL4 overexpression predicted favorable PFS (P = 0.021) in patients with LUSC, but patients with high CCL4 levels in LUAD had shorter OS (P = 0.013). Conclusion: Our study revealed that CCL2 and CCL4 expression levels could serve as potential prognostic biomarkers and therapeutic targets for NSCLC patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the distinct presence of EBV microRNAs in serum could aid in screening endemic regions for NPC. A proposed network of genes targeted by these microRNAs could also shed light on EBV-associated tumorigenesis. METHODS: MicroRNA microarray profiling of 5 paired NPC biopsies was followed by validation of 12 up-regulated EBV microRNAs (BART1-3p, 2-5p, 5, 6-5p, 6-3p, 7, 8, 9, 14, 17-5p, 18-5p, 19-3p) in 15 additional cases by real-time polymerase chain reaction. Tumor (cellular) and serum microRNA copy numbers from the same 15 patients were correlated. Expression of the same microRNAs were also examined in EBV-positive cell lines C666 and NP460hTERT+EBV. Bioinformatic tools helped predict cellular target genes, which were later confirmed by gene expression analysis. RESULTS: The authors' high-throughput approach shows that EBV microRNAs are generally more up-regulated than microRNAs of human origin. Twenty-nine of 39 EBV microRNAs were significantly up-regulated in tumor versus their nontumor biopsies ( P < .05). Upon successfully validating 12 selected EBV microRNAs in 15 additional paired NPC cases, the authors found that their distinct presence in the serum of NPC patients positively correlated with cellular copy numbers of EBV microRNAs. Further investigation of potential EBV microRNA target genes revealed inhibition of tumor suppressor genes (eg, PTEN) and extensive deregulation of several pathways frequently involved in NPC (eg, Wnt signaling). CONCLUSIONS: Increasing knowledge of host-virus interaction via microRNAs may provide feasible explanations underlying NPC tumorigenesis along with the development of biomarkers for screening high-risk populations. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Our recent studies suggested that the chromodomain helicase DNA binding protein 1-like (CHD1L) gene plays an oncogenic role in human hepatocellular carcinoma. However, the status of CHD1L protein expression in ovarian cancer and its clinical/prognostic significance are obscure. Methods: In this study, immunohistochemistry (IHC) for CHD1L was performed on a tissue microarray (TMA) containing 102 primary ovarian carcinomas and 44 metastatic lesions (omental metastasis). Receiver-operator curve (ROC) analysis was used to evaluate patients’ survival status. Results: There is an augmented tendency of CHD1L expression in ovarian carcinoma metastasis than in primary lesions (P<0.05). A significant association was found between positive expression of CHD1L and tumors histological type (P <0.05). By univariate survival analysis of the ovarian carcinoma cohorts, positive expression of CHD1L was significantly correlated with shortened patient survival (mean 66.7 months versus 97.4 months, P<0.05). Moreover, CHD1L expression was evaluated to be a significant and independent prognostic factor in multivariate analysis (P<0.05). Conclusions: These findings provide evidence that positive expression of CHD1L protein is significantly correlated with the metastasis proceeding of ovarian carcinoma, and CHD1L protein expression, as examined by IHC, may act as a novel prognostic biomarker for patients with ovarian carcinoma. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Profiling of Epstein-BarrVirus-Encoded MicroRNAs inNasopharyngeal CarcinomaReveals Potential Biomarkersand Oncomirs," by Wong AM, Kong KL and colleagues is presented and also includes the reply from the author.

[Display omitted] Tumors are intricate ecosystems containing malignant components that generate adaptive and evolutionarily driven abnormal tissues. Through self-renewal and differentiation, cancers are reconstructed by a dynamic subset of stem-like cells that enforce tumor heterogeneity and remodel the tumor microenvironment (TME). Through recent technology advances, we are now better equipped to investigate the fundamental role of cancer stem cells (CSCs) in cancer biology. In this review, we discuss the latest insights into characteristics, markers and mechanism of CSCs and describe the crosstalk between CSCs and other cells in TME. Additionally, we explore the performance of single-cell sequencing and spatial transcriptome analysis in CSCs studies and summarize the therapeutic strategies to eliminate CSCs, which could broaden the understanding of CSCs and exploit for therapeutic benefit. [ABSTRACT FROM AUTHOR]

Abstract: Non-small cell lung cancer (NSCLC) accounts for approximately 70% of all lung cancer-related deaths worldwide. Prognostic markers are essential for the early detection of lung cancer in patients. In this study, we first identified microRNA146 (miR-146) expression in cancer cell lines using miRNA in situ hybridization (MISH) and confirmed the accuracy of MISH using q-RT-PCR. In addition, two different systems, BCIP/NBT and ELF, were used to detect the signal for a comparative analysis of the specificity of MISH. Compared to the BCIP/NBT system, the ELF detection system was more effective for MISH. Furthermore we detected the expression of miR-146 in NSCLC tissues (43 cases) and normal tissues (32 cases). Based on our results, we can conclude that miR-146 is more highly expressed in cancer tissue than normal tissue (t-test, P<0.05) and that miR-146 can predict the prognosis of NSCLC by MISH. Our findings preliminary demonstrate that MISH can be applied as a molecular diagnostic tool to determine the expression and localization of miRNAs in cancer tissues and that miR-146, determined by MISH, predicts the prognosis of NSCLC patients. [Copyright &y& Elsevier]