title: Overexpression of microRNA-21 regulating PDCD4 during tumorigenesis of liver fluke-associated cholangiocarcinoma contributes to tumor growth and metastasis.
abstract: MicroRNA, an endogenous noncoding RNA modulating gene expression, is a key molecule that by its dysregulation plays roles in inflammatory-driven carcinogenesis. This study aimed to investigate the role of oncomiR miR-21 and its target, the programmed cell death 4 (PDCD4) in tumor growth and metastasis of the liver fluke Opisthorchis viverrini-associated cholangiocarcinoma (CCA). The expression levels of miR-21 and PDCD4 were analyzed using the TaqMan miRNA expression assay and immunohistochemistry in liver tissues of both O. viverrini plus N-nitrosodimethylamine (NDMA)-treated hamsters and human CCA samples (n=23 cases). The functional assay for miR-21 was performed in CCA cell lines by the anti-miR-21 and pre-miR-21 transfection procedures. The peak of miR-21 levels were reached at 2 (hyperplastic lesions) and 6 (CCA) months of the O. viverrini plus NDMA-induced group and had a reverse response with its target PDCD4 proteins. In human CCA, miR-21 was overexpressed in tumor tissues when compared with nontumor tissues (P=0.0034) and had a negative correlation with PDCD4 protein (P=0.026). It was also found that high expression of miR-21 was significantly correlated with shorter survival (P<0.05) and lymph node metastasis (P=0.037) of CCA patients. Transient transfection of pre-miR-21 reduced the PDCD4 level and resulted in an increase of M213 CCA cell growth and wound-induced migration ability. These results indicated that miR-21 plays a role in the carcinogenesis and metastasis of O. viverrini-associated CCA by suppressing the function of PDCD4. Modulation of aberrantly expressed miR-21 may be a useful strategy to inhibit tumor cell phenotypes or improve response to chemotherapy.
authors: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors: P
authors: P
authors: Chusorn
authors: N
authors: N
authors: Namwat
authors: W
authors: W
authors: Loilome
authors: A
authors: A
authors: Techasen
authors: C
authors: C
authors: Pairojkul
authors: N
authors: N
authors: Khuntikeo
authors: A
authors: A
authors: Dechakhamphu
authors: C
authors: C
authors: Talabnin
authors: W
authors: W
authors: Chan-On
authors: C K
authors: CK
authors: Ong
authors: B T
authors: BT
authors: Teh
authors: P
authors: P
authors: Yongvanit
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001652:Bile Ducts / Q000469:parasitology / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000209:etiology* / Q000378:metabolism / Q000556:secondary; D006224:Cricetinae; D005210:Fasciola hepatica / Q000472:pathogenicity; D005211:Fascioliasis / Q000150:complications* / Q000235:genetics / Q000469:parasitology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008647:Mesocricetus; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009889:Opisthorchiasis / Q000235:genetics / Q000469:parasitology / Q000473:pathology; D009891:Opisthorchis / Q000472:pathogenicity; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins