Nannan Han1, Hao Lu2, Zun Zhang3, Min Ruan4, Wenjun Yang2, Chenping Zhang2. 1. Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai 200011, China; Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Fengcheng Hospital, Fengxian District, Shanghai 201400, China. 2. Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai 200011, China. 3. Department of Stomatology, Shanghai East Hospital, Tongji University, Shanghai 200120, China. Electronic address: zz5609@easthospital.cn. 4. Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai 200011, China; Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Fengcheng Hospital, Fengxian District, Shanghai 201400, China. Electronic address: RUANM1740@sh9hospital.org.
Abstract
OBJECTIVES: To conduct an integrated analysis of microRNA and mRNA expression profile and further discover vital molecules to uncover novel pathogenic mechanisms in salivary adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: MicroRNA and mRNA expression profiles were obtained from six paired primary SACC tumors and corresponding adjacent normal glands using high-throughput next-generation sequencing technology followed by an overall integrated bioinformatics analysis and subsequently molecular biology techniques validation. RESULTS: Compared with adjacent noncancerous normal gland, 2107 significant differentially expressed mRNA were determined in SACC. Gene ontology and KEGG pathway analysis suggested that the differentially expressed genes were relevant to many significant biological implications. Venn diagram analysis of differentially expressed genes in different group identified 29 differentially expressed overlapping mRNA. 40 differentially expressed microRNAs were also identified in SACC. Furthermore, integrated analysis of microRNA and mRNA expression profiles recognized a core microRNA-mRNA regulatory network and unmasked many novel genes including SCUBE3, CA6, hsa-miR-885-5p and other molecules which may play an essential role in the carcinogenesis of SACC. Also, Q-PCR and immunohistochemistry results reveal the high expression and distribution of SCUBE3 in SACC and dual luciferase reporter assay also preliminarily validated that SCUBE3 was a target of hsa-miR-885-5p. CONCLUSION: Contemporary microRNA/mRNA analysis have uncovered many mRNAs and microRNAs worthy further exploration in SACC. These are bound to help us shed light on the overall genetic background of SACC and further elucidate the potential molecular mechanism of SACC.
OBJECTIVES: To conduct an integrated analysis of microRNA and mRNA expression profile and further discover vital molecules to uncover novel pathogenic mechanisms in salivary adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: MicroRNA and mRNA expression profiles were obtained from six paired primary SACC tumors and corresponding adjacent normal glands using high-throughput next-generation sequencing technology followed by an overall integrated bioinformatics analysis and subsequently molecular biology techniques validation. RESULTS: Compared with adjacent noncancerous normal gland, 2107 significant differentially expressed mRNA were determined in SACC. Gene ontology and KEGG pathway analysis suggested that the differentially expressed genes were relevant to many significant biological implications. Venn diagram analysis of differentially expressed genes in different group identified 29 differentially expressed overlapping mRNA. 40 differentially expressed microRNAs were also identified in SACC. Furthermore, integrated analysis of microRNA and mRNA expression profiles recognized a core microRNA-mRNA regulatory network and unmasked many novel genes including SCUBE3, CA6, hsa-miR-885-5p and other molecules which may play an essential role in the carcinogenesis of SACC. Also, Q-PCR and immunohistochemistry results reveal the high expression and distribution of SCUBE3 in SACC and dual luciferase reporter assay also preliminarily validated that SCUBE3 was a target of hsa-miR-885-5p. CONCLUSION: Contemporary microRNA/mRNA analysis have uncovered many mRNAs and microRNAs worthy further exploration in SACC. These are bound to help us shed light on the overall genetic background of SACC and further elucidate the potential molecular mechanism of SACC.