title: miR-16 induction after CDK4 knockdown is mediated by c-Myc suppression and inhibits cell growth as well as sensitizes nasopharyngeal carcinoma cells to chemotherapy.
abstract: Cyclin-dependent kinase 4 (CDK4) is a member of cyclin-dependent kinase family which regulates G1 to S cell cycle transition. CDK4 activity is increased in many tumor types. Here, we report a negative automodulatory feedback loop between CDK4 and miR-16 that regulates cell cycle progression in nasopharyngeal carcinoma (NPC). By miRNA array and real-time PCR, we identified upregulation of tumor suppressor miR-16a, which inhibited cell cycle progression and sensitized NPC cells to chemotherapy. CDK4 knockdown reduced the expression of c-Myc, the latter of which directly suppresses the miR-16 expression by directly binding to the miR-16 promoter. Moreover, we found that miR-16 upregulation could reduce CDK4 expression by repressing CCND1 and thus forms a feedback loop via the CDK4/c-Myc/miR-16/CCND1 pathway. Finally, miR-16 was negatively correlated with CDK4 expression in NPC biopsies. In summary, our results define a double-negative feedback loop involving CDK4 and miR-16 mediated by c-Myc that modulates NPC cell growth and chemotherapy sensitivity.
authors.affiliation: Department of Pathology, Third affiliated hospital, Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Department of Pathology, Guangzhou Medical University, Guangzhou, 510282, China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Department of Pathology, Guangzhou Medical University, Guangzhou, 510282, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Third affiliated hospital, Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Department of Pathology, Guangzhou Medical University, Guangzhou, 510282, China.
authors.forename: Qiulian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, Third affiliated hospital, Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Department of Pathology, Guangzhou Medical University, Guangzhou, 510282, China.
authors.forename: Ruichao
authors.initials: R
authors.lastname: Chen
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Long
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou, 510515, China. fangweiyi1975@163.com.|Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong, 510315, China. fangweiyi1975@163.com.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Fang
authors.affiliation: Department of Pathology, Third affiliated hospital, Guangzhou Medical University, Guangzhou, 510150, China. narcissus_jane@163.com.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China. narcissus_jane@163.com.|Department of Pathology, Guangzhou Medical University, Guangzhou, 510282, China. narcissus_jane@163.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: CDK4; Feedback loop; NPC; c-Myc; miR-16