title: Increased miR-221 expression in hepatocellular carcinoma tissues and its role in enhancing cell growth and inhibiting apoptosis in vitro.
abstract: BACKGROUND
  MiR-221 is over-expressed in human hepatocellular carcinoma (HCC), but its clinical significance and function in HCC remains uncertain. The aim of the study was to investigate the relationship between miR-221 overexpression and clinicopathological parameters in HCC formalin-fixed paraffin-embedded (FFPE) tissues, and the effect of miR-221 inhibitor and mimic on different HCC cell lines in vitro.
  
  
  METHODS
  MiR-221 expression was detected using real time RT-qPCR in FFPE HCC and the adjacent noncancerous liver tissues. The relationship between miR-221 level and clinicopathological features was also analyzed. Furthermore, miR-221 inhibitor and mimic were transfected into HCC cell lines HepB3, HepG2 and SNU449. The effects of miR-221 on cell growth, cell cycle, caspase activity and apoptosis were also investigated by spectrophotometry, fluorimetry, fluorescence microscopy and flow cytometry, respectively.
  
  
  RESULTS
  The relative expression of miR-221 in clinical TNM stages III and IV was significantly higher than that in the stages I and II. The miR-221 level was also upregulated in the metastatic group compared to the nonmetastatic group. Furthermore, miR-221 over-expression was related to the status of tumor capsular infiltration in HCC clinical samples. Functionally, cell growth was inhibited, cell cycle was arrested in G1/S-phase and apoptosis was increased by miR-221 inhibitor in vitro. Likewise, miR-221 mimic accelerated the cell growth.
  
  
  CONCLUSIONS
  Expression of miR-221 in FFPE tissues could provide predictive significance for prognosis of HCC patients. Moreover, miR-221 inhibitor could be useful to suppress proliferation and induce apoptosis in HCC cells. Thus miR-221 might be a critical targeted therapy strategy for HCC.
authors: Research Department, Affiliated Cancer Hospital, Guangxi Medical University, 71 Hedi Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China. tourtair@163.com
authors: Minhua
authors: M
authors: Rong
authors: Gang
authors: G
authors: Chen
authors: Yiwu
authors: Y
authors: Dang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D018572:Disease-Free Survival; D005260:Female; D005404:Fixatives; D005434:Flow Cytometry; D005470:Fluorometry; D005557:Formaldehyde; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016707:Tissue Fixation; D014162:Transfection; D015854:Up-Regulation
chemical_list: D053148:Caspase 3; D053179:Caspase 7; D005404:Fixatives; D005557:Formaldehyde; D035683:MicroRNAs; C525709:MIR221, human; C505407:CASP3 protein, human; C505520:CASP7 protein, human