Search

Additional file 1. Figure S1. CNE2-EBV-GFP infection of Akata cells was determined by FCM and HCIS. Figure S2. Neutralizing titers of 12 rhesus macaque sera against CNE2-EBV-GFP virus infection of B cells determined by FCM and HCIS. Figure S3. Anti-gp350 IgG titer in rhesus macaque monkey sera and its correlation with B cell neutralizing titer. Figure S4. Akata-EBV-GFP infection of HNE1 cells was determined by FCM and HCIS. Figure S5. Neutralizing activity of CL59 determined by FCM and HCIS.

Additional file 2. Full images of the western blotting results (Fig. S14-S15).

Additional file 1. Supplementary methods, figures (Figures S1-S13) and tables (Tables S1-S9).

Tian-Liang Xia,* Shu-Mei Yan,* Li Yuan, Mu-Sheng Zeng State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mu-Sheng Zeng Email zengmsh@sysucc.org.cnBackground: The N6-methyladenosine (m6A) RNA modification of mRNA mediates various cellular functions and cancer progression. However, the roles of m6A RNA modification in the regulation of esophageal squamous cell carcinoma (ESCC), the dominant subtype of esophageal cancer in Asia, were unclear.Materials and Methods: Here, we analyzed the mRNA expression level of methyltransferase like 3 (METTL3) in the public available datasets of ESCC tissues and matched adjacent normal tissues. We also performed immunohistochemistry (IHC) assays to detect the protein expression of METTL3 in human ESCC tissue specimen. In our study, we also analyzed the association between METTL3 expression and prognosis using Cox proportional hazard regression in 207 ESCC patients.Results: The results of public available datasets and IHC assays showed that METTL3 was upregulated in tumor compared with adjacent nonmalignant esophageal mucosal tissues. The IHC results indicated that higher expression level of METTL3 was associated with worse survival. We also found that METTL3 expression level was an independent predictor for disease-free survival and overall survival of ESCC patients.Conclusion: Our results revealed that the METTL3 expression level could be used as an independent prognostic biomarker for ESCC prognosis.Keywords: esophageal squamous cell carcinoma, METTL3, prognosis, survival

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.