title: miR-26a and its target CKS2 modulate cell growth and tumorigenesis of papillary thyroid carcinoma.
abstract: BACKGROUND
  While many studies have shown that levels of miR-26a are lower in papillary thyroid carcinoma (PTC), the role and mechanism of miR-26a in PTC are unclear.
  
  
  METHODS
  We used database searches to select potential mRNA targets of miR-26a. Anti-miR-26a, miR-26a mimic, siRNA for CKS2 and their effects on cell growth, cell-cycle distribution and colony formation were evaluated. We also evaluate the over-expressed miR-26a in TPC-1 cells in severe combined immune-deficient mice. We used luciferase reporter assays, real-time PCR and western blot analysis to measure the expression and activity of miR-26a, CKS2, and related factors such as cyclin B1, cyclin A, cdk1, bcl-xl and Akt. Finally, we measured the relationship between the levels of miR-26a and CKS2 in PTC and normal thyroid tissues.
  
  
  RESULTS
  Relative to normal thyroid tissues, miR-26a is consistently down-regulated in TPC specimens, and CKS2 was identified as a potential target. Up-regulated miR-26a expression or down-regulated CKS2 expression in TPC-1 and CGTH W3 cells lines caused G2 phase-arrest. Decreased miR-26a expression or increased CKS2 expression could have inverse function on PTC cell lines. CyclinB1, cyclinA, bcl-xl and AKt are indirectly regulated by miR-26a in a CKS2-dependent manner. Finally, CKS2 is overexpressed in PTC specimens relative to normal thyroid tissue, and a significant inverse correlation exists between miR-26a and CKS2 expression in clinical PTC specimens.
  
  
  CONCLUSIONS
  Our data indicate that miR-26a functions as a growth-suppressive miRNA in PTC, and that its suppressive effects are mediated mainly by repressing CKS2 expression.
authors.affiliation: Department of Nuclear Medicine, Shanghai 10th People's Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Lv
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Maoquan
authors.initials: M
authors.lastname: Li
authors.forename: Quanchi
authors.initials: Q
authors.lastname: Chen
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
authors.forename: Wenqing
authors.initials: W
authors.lastname: Liang
authors.forename: Lanbao
authors.initials: L
authors.lastname: Ding
authors.forename: Haidong
authors.initials: H
authors.lastname: Cai
authors.forename: Da
authors.initials: D
authors.lastname: Fu
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Lv
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D042846:CDC2-CDC28 Kinases / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D018874:Spheroids, Cellular; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D047368:Tumor Burden / Q000235:genetics; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D035683:MicroRNAs; C528163:MIRN26 microRNA, human; C083689:CKS2 protein, human