title: Roles of miR-196a on gene regulation of neuroendocrine tumor cells.
abstract: This study aims at investigating miR-196a roles using in vitro models. miR-196a was detected in small intestinal neuroendocrine tumors (SI-NETs) and lung NETs. miR-196a target prediction analysis suggested HOXA9, HOXB7, LRP4 and RSPO2 genes for further investigation. The level of these four genes is detectable in SI-NET tissue specimens at different disease stages and serum samples of untreated and somatostatin analogs treated patients with liver metastases. A miR-196a inhibitor was used to silence its effects in NET cells. We show that the four target genes were significantly upregulated at transcriptional level in silenced NET cells. HOXA9, HOXB7, LRP4 and RSPO2 encoded proteins are also upregulated at translational level in miR-196a silenced NET cells. miR-196a downstream genes BMP4, ETS1, CTNNB1, FZD5, LRP5 and LRP6 were significantly upregulated at transcriptional level in miR-196a silenced CNDT2.5 and NCI-H727 cells. In addition, miR-196a clearly does not play a role in NET cell growth control.
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Su-Chen
authors.initials: SC
authors.lastname: Li
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Hao
authors.initials: H
authors.lastname: Shi
authors.affiliation: Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital, London, UK; The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Mohid
authors.initials: M
authors.lastname: Khan
authors.affiliation: Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital, London, UK.
authors.forename: Martyn
authors.initials: M
authors.lastname: Caplin
authors.affiliation: Department of Oncology, UCL Cancer Institute, University College London, London, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Meyer
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Science for Life Laboratory,Endocrine Oncology Clinic, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Öberg
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Science for Life Laboratory,Endocrine Oncology Clinic, Uppsala University Hospital, Uppsala, Sweden. Electronic address: valeria.giandomenico@medsci.uu.se.
authors.forename: Valeria
authors.initials: V
authors.lastname: Giandomenico
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000378:metabolism; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D034622:RNA Interference; D000098907:R-Spondins
chemical_list: D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D026502:LDL-Receptor Related Proteins; D035683:MicroRNAs; C490538:HOXB7 protein, human; C551781:LRP4 protein, human; C542543:MIRN196 microRNA, human; C557408:Rspo2 protein, human; D000098907:R-Spondins; C097899:homeobox protein HOXA9
keywords: MicroRNA inhibitors; Neuroendocrine tumor cells; Transfection effects; miR-196a target genes