PMID- 30453289 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20220430 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 51 IP - 1 DP - 2018 TI - MicroRNA-197 Promotes Metastasis of Hepatocellular Carcinoma by Activating Wnt/beta-Catenin Signaling. PG - 470-486 LID - 10.1159/000495242 [doi] AB - BACKGROUND/AIMS: MicroRNA-197 (miR-197) has been shown to play roles in epithelialmesenchymal transition (EMT) and metastasis. The Wnt/beta-catenin pathway is associated with EMT, but whether miR-197 regulatesWnt/beta-catenin remains unclear. This study was to demonstrate the role of miR-197 on the Wnt/beta-catenin pathway in hepatocellular carcinoma (HCC). METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-197 in 105 HCC specimens and 15 HCC cell lines. We tested the predicted target gene of miR-197 using a genetic report system. The role of miR-197 in HCC cell invasion and migration (wound healingand cell invasion and migrationby Transwell assays) and in an HCC xenograft modelwas analyzed. RESULTS: Using a miRNA microarray analysis of HCC specimens and compared with non-metastatic HCC, miR-197 was identified as one of the most upregulated miRNAs in metastatic HCC. miR-197 expression was positively associated with the invasiveness of HCC cell lines. Metastatic HCC cells with high miR-197 expression had Wnt/beta-catenin signaling activation. High levels of miR-197 expression also promoted EMT and invasionHCC cells in vitro and in vivo. miR-197 directly targeted Axin-2, Naked cuticle 1 (NKD1), and Dickkopf-related protein 2 (DKK2), leading to inhibition of Wnt/beta-catenin signaling. High miR-197 expression was found in HCC specimens from patients with portal vein metastasis;high miR-197 expression correlated to the expression of Axin2, NKD1, and DKK2. CONCLUSION: miR-197 promotes HCC invasion and metastasis by activating Wnt/beta-catenin signaling. miR-197 could possibly be used as a prognostic marker and therapeutic target for HCC. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - Hu, Zhaoxia AU - Hu Z AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. AD - Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China. AD - Guangdong Provincial Key Laboratory of Liver Disease, Guangzhou, China. FAU - Wang, Peipei AU - Wang P AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. FAU - Lin, Jiaxin AU - Lin J AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. FAU - Zheng, Xingrong AU - Zheng X AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. FAU - Yang, Fangji AU - Yang F AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. FAU - Zhang, Genglin AU - Zhang G AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. FAU - Chen, Dabiao AU - Chen D AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. FAU - Xie, Junqiang AU - Xie J AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. FAU - Gao, Zhiliang AU - Gao Z AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. AD - Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China. AD - Guangdong Provincial Key Laboratory of Liver Disease, Guangzhou, China. FAU - Peng, Liang AU - Peng L AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. FAU - Xie, Chan AU - Xie C AD - Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Chinaxchan@mail.sysu.edu.cn. AD - Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Chinaxchan@mail.sysu.edu.cn. AD - Guangdong Provincial Key Laboratory of Liver Disease, Guangzhou, Chinaxchan@mail.sysu.edu.cn. LA - eng PT - Journal Article DEP - 20181119 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (3' Untranslated Regions) RN - 0 (AXIN2 protein, human) RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Antagomirs) RN - 0 (Axin Protein) RN - 0 (Calcium-Binding Proteins) RN - 0 (Carrier Proteins) RN - 0 (DKK2 protein, human) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (MIRN197 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NKD1 protein, human) RN - 0 (RNA, Small Interfering) SB - IM EIN - Cell Physiol Biochem. 2022 Apr 30;56(2):229. PMID: 35488525 MH - 3' Untranslated Regions MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Antagomirs/metabolism/therapeutic use MH - Axin Protein/antagonists & inhibitors/genetics/metabolism MH - Calcium-Binding Proteins MH - Carcinoma, Hepatocellular/drug therapy/genetics/*pathology MH - Carrier Proteins/antagonists & inhibitors/genetics/metabolism MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Epithelial-Mesenchymal Transition MH - Humans MH - Intercellular Signaling Peptides and Proteins/chemistry/genetics/metabolism MH - Liver Neoplasms/drug therapy/genetics/*pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - MicroRNAs/antagonists & inhibitors/genetics/*metabolism MH - RNA Interference MH - RNA, Small Interfering/metabolism MH - *Wnt Signaling Pathway OTO - NOTNLM OT - EMT OT - Hepatocellular carcinoma OT - Metastasis OT - MicroRNA OT - Wnt/b-catenin EDAT- 2018/11/20 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/11/20 06:00 PHST- 2018/04/28 00:00 [received] PHST- 2018/11/09 00:00 [accepted] PHST- 2018/11/20 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/11/20 06:00 [entrez] AID - 000495242 [pii] AID - 10.1159/000495242 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;51(1):470-486. doi: 10.1159/000495242. Epub 2018 Nov 19.