Increased miR-221 expression in hepatocellular carcinoma tissues and its role in enhancing cell growth and inhibiting apoptosis in vitro

• Published in: BMC cancer 2013-01, Vol.13 (1), p.21-21, Article 21
• Main Authors: Rong, Minhua, Chen, Gang, Dang, Yiwu
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Analysis of Variance; Apoptosis; Biological markers; Biomarkers; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - therapy; Care and treatment; Caspase; Caspase 3 - metabolism; Caspase 7 - metabolism; Cell adhesion & migration; Cell cycle; Cell growth; Cell Proliferation; Cell Survival; Cyclin-dependent kinases; Development and progression; Disease-Free Survival; Epidermal growth factor; Experiments; Female; Fixatives; Flow Cytometry; Fluorescence microscopy; Fluorometry; Formaldehyde; G1 Phase Cell Cycle Checkpoints; Gene expression; Gene Expression Regulation, Neoplastic; Growth; Hep G2 Cells; Hepatocellular carcinoma (HCC); Hepatoma; Humans; Liver; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - therapy; Male; Medical research; MicroRNA; MicroRNAs - metabolism; Microscopy, Fluorescence; Middle Aged; MiR-221; Neoplasm Invasiveness; Neoplasm Staging; Paraffin Embedding; Physiological aspects; Real time; Real-Time Polymerase Chain Reaction; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Statistical analysis; Time Factors; Tissue Fixation; Transfection; Tumors; Up-Regulation
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-13-21

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. 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. 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. 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.