title: An integrative transcriptomic analysis reveals p53 regulated miRNA, mRNA, and lncRNA networks in nasopharyngeal carcinoma.
abstract: It has been reported that p53 dysfunction is closely related to the carcinogenesis of nasopharyngeal carcinoma (NPC). Recently, an increasing body of evidence has indicated that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) participate in p53-associated signaling pathways and, in addition to mRNAs, form a complex regulation network to promote tumor occurrence and progression. The aim of this study was to elucidate the p53-regulated miRNAs, mRNAs, and lncRNAs and their regulating networks in NPC. Firstly, we overexpressed p53 in the NPC cell line HNE2 and performed transcriptomic gene expression profiling (GEP) analysis, which included miRNAs, mRNAs, and lncRNAs, using microarray technology at 0, 12, 24, and 48 h after transfection. There were 38 miRNAs (33 upregulated and 5 downregulated), 2107 mRNAs (296 upregulated and 1811 downregulated), and 1190 lncRNAs (133 upregulated and 1057 downregulated) that were significantly dysregulated by p53. Some of the dysregulated molecules were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Then, we integrated previously published miRNAs, mRNAs, and lncRNAs GEP datasets from NPC biopsies to investigate the expression of these p53 regulated molecules and found that 7 miRNAs, 218 mRNAs, and 101 lncRNAs regulated by p53 were also differentially expressed in NPC tissues. Finally, p53-regulated miRNA, mRNA, and lncRNA networks were constructed using bioinformatics methods. These miRNAs, mRNAs, and lncRNAs may participate in p53 downstream signaling pathways and play important roles in the carcinogenesis of NPC. Thorough investigations of their biological functions and regulating relationships will provide a novel view of the p53 signaling pathway, and the restoration of p53 functioning or its downstream gene regulating network is potentially of great value in treating NPC patients.
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.|School of Nursing, Hunan Polytechnic of Environment and Biology, Hengyang, Hunan, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China. zengzhaoyang@csu.edu.cn.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China. zengzhaoyang@csu.edu.cn.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. zengzhaoyang@csu.edu.cn.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.affiliation: Clinical Research Institution, the First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zu
authors.affiliation: Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiang
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53
keywords: Gene regulating network; Long noncoding RNAs (lncRNAs); Nasopharyngeal carcinoma (NPC); mRNAs; microRNAs (miRNAs); p53