|Title:||Lin-28B expression promotes transformation and invasion in human hepatocellular carcinoma||Authors:||Wang Y.-C.
|Issue Date:||2010||Journal Volume:||31||Journal Issue:||9||Start page/Pages:||1516-1522||Source:||Carcinogenesis||Abstract:||
MicroRNAs (miRNAs) play critical roles in embryonic development and are frequently deregulated in human cancers. The let-7 family members are tumor-suppressing miRNAs and are frequently downregulated in cancer cells. Lin-28 and Lin-28B are RNA-binding proteins highly expressed in embryonic tissues. Lin-28 proteins block let-7 precursors from being processed to mature miRNAs by inducing terminal uridylation and degradation of let-7 precursors. Here, we report that Lin-28B, but not Lin-28, is highly expressed in hepatocellular carcinoma (HCC). Lin-28B expression was more frequently noted in high-grade HCCs with high α-fetoprotein levels. Knockdown of Lin-28B by RNA interference in the HCC cell line HCC36 suppressed proliferation in vitro and reduced in vivo tumor growth in NOD/SCID mice. In contrast, overexpression of Lin-28B in the HCC cell line HA22T enhanced tumorigenicity. Overexpression of Lin-28B also induced epithelial-mesenchymal transition in HA22T cells and hence, invasion capacity. Large-scale real-time PCR array analysis revealed that, among 380 miRNAs, only let-7/mir-98 family members were regulated by Lin-28B. Lin-28B overexpression enhanced the expression of the known let-7 targets c-myc and HMGA2. It was also found that Lin-28B enhanced the expression of type 1 insulin-like growth factor receptor in a let-7-dependent manner. These results indicate that Lin-28B regulates tumor formation and invasion in HCC through coordinated repression of the let-7/mir-98 family and induction of multiple oncogenic pathways. ? The Author 2010. Published by Oxford University Press. All rights reserved.
|ISSN:||0143-3334||DOI:||10.1093/carcin/bgq107||SDG/Keyword:||alpha fetoprotein; high mobility group A2 protein; Lin 28 protein; Lin 28B protein; microRNA; microRNA 98; Myc protein; protein let 7; regulator protein; somatomedin C receptor; unclassified drug; untranslated RNA; adolescent; adult; aged; animal experiment; animal model; article; cancer cell culture; cancer invasion; carcinogenicity; cell invasion; cell proliferation; cell transformation; controlled study; disease severity; epithelial mesenchymal transition; female; gene expression; gene overexpression; gene repression; gene targeting; histopathology; human; human cell; human tissue; in vitro study; in vivo study; liver carcinogenesis; liver cell carcinoma; liver resection; major clinical study; male; microarray analysis; mouse; nonhuman; nucleotide sequence; priority journal; protein blood level; protein expression; real time polymerase chain reaction; RNA interference; signal transduction; tumor growth; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Apoptosis; Blotting, Western; Carcinoma, Hepatocellular; Cell Adhesion; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; HMGA2 Protein; Humans; Liver Neoplasms; Male; Mice; Mice, Inbred NOD; Mice, SCID; MicroRNAs; Middle Aged; Neoplasm Invasiveness; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA-Binding Proteins; Xenograft Model Antitumor Assays; Young Adult
|Appears in Collections:||病理學科所|
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