title: MicroRNA-215 functions as a tumor suppressor and directly targets ZEB2 in human pancreatic cancer.
abstract: It has been shown that microRNA-215 (miR-215) is dysregulated in several human malignancies, and this correlates with tumor progression. However, its expression and function in pancreatic cancer is still unclear. The aim of this study was to explore the effects of miR-215 on pancreatic cancer formation and progression. Using quantitative RT-PCR, we detected miR-215 expression in pancreatic cancer cell lines and primary tumor tissues. The association of miR-215 expression with clinicopathological factors and prognosis was also analyzed. We then observed the effects of miR-215 on the biological behavior of pancreatic cancer cells. Lastly, the potential regulatory function of miR-215 on ZEB2 expression was investigated. miR-215 expression levels were significantly downregulated in pancreatic cancer samples and cell lines. Decreased miR-215 expression was significantly associated with large tumor size, advanced TNM stage, lymph node metastasis, vessel invasion, and lower overall survival. Multivariate regression analysis corroborated that downregulation of miR-215 was an independent unfavorable prognostic factor. Overexpression of miR-215 inhibited pancreatic cancer cell proliferation, invasion, and migration; promoted cell apoptosis in vitro; and suppressed tumorigenicity in vivo. Further, ZEB2 was confirmed as a direct target of miR-215 by using a luciferase reporter assay. These findings indicate that miR-215 may act as a tumor suppressor in pancreatic cancer cells, and could serve as a novel therapeutic target for miR-based therapy.
authors.affiliation: Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Q W
authors.initials: QW
authors.lastname: Li
authors.affiliation: Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: C B
authors.initials: CB
authors.lastname: Liu
authors.affiliation: Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: K R
authors.initials: KR
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: K W
authors.initials: KW
authors.lastname: Hu
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D047368:Tumor Burden; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; C553667:MIRN215 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2