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Identification of microRNAs specific for epithelial cell adhesion molecule-positive tumor cells in hepatocellular carcinoma.
Ji, Junfang; Zheng, Xin; Forgues, Marshonna; Yamashita, Taro; Wauthier, Eliane L; Reid, Lola M; Wen, Xinyu; Song, Young; Wei, Jun S; Khan, Javed; Thorgeirsson, Snorri S; Wang, Xin Wei.
Afiliação
  • Ji J; Life Sciences Institute, Zhejiang University, Hangzhou, China.
  • Zheng X; University of Hawaii Cancer Center, Cancer Biology Program (Ji), Epidemiology Program (Zheng), Honolulu, HI.
  • Forgues M; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
  • Yamashita T; University of Hawaii Cancer Center, Cancer Biology Program (Ji), Epidemiology Program (Zheng), Honolulu, HI.
  • Wauthier EL; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
  • Reid LM; Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.
  • Wen X; Department of Cell Biology and Physiology and Program in Molecular Biology and Biotechnology, UNC School of Medicine, Chapel Hill, NC.
  • Song Y; Department of Cell Biology and Physiology and Program in Molecular Biology and Biotechnology, UNC School of Medicine, Chapel Hill, NC.
  • Wei JS; Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
  • Khan J; Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
  • Thorgeirsson SS; Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
  • Wang XW; Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
Hepatology ; 62(3): 829-40, 2015 Sep.
Article em En | MEDLINE | ID: mdl-25953724
ABSTRACT
UNLABELLED Therapies that target cancer stem cells (CSCs) hold promise in eliminating cancer burden. However, normal stem cells are likely to be targeted owing to their similarities to CSCs. It is established that epithelial cell adhesion molecule (EpCAM) is a biomarker for normal hepatic stem cells (HpSCs), and EpCAM(+) AFP(+) hepatocellular carcinoma (HCC) cells have enriched hepatic CSCs. We sought to determine whether specific microRNAs (miRNAs) exist in hepatic CSCs that are not expressed in normal HpSCs. We performed a pair-wise comparison of the miRNA transcriptome of EpCAM(+) and corresponding EpCAM(-) cells isolated from two primary HCC specimens, as well as from two fetal livers and three healthy adult liver donors by small RNA deep sequencing. We found that miR-150, miR-155, and miR-223 were preferentially highly expressed in EpCAM(+) HCC cells, which was further validated. Their gene surrogates, identified using miRNA and messenger RNA profiling in a cohort of 292 HCC patients, were associated with patient prognosis. We further demonstrated that miR-155 was highly expressed in EpCAM(+) HCC cells, compared to corresponding EpCAM(-) HCC cells, fetal livers with enriched normal hepatic progenitors, and normal adult livers with enriched mature hepatocytes. Suppressing miR-155 resulted in a decreased EpCAM(+) fraction in HCC cells and reduced HCC cell colony formation, migration, and invasion in vitro. The reduced levels of identified miR-155 targets predicted the shortened overall survival and time to recurrence of HCC patients.

CONCLUSION:

miR-155 is highly elevated in EpCAM(+) HCC cells and might serve as a molecular target to eradicate the EpCAM(+) CSC population in human HCCs.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Moléculas de Adesão Celular / Regulação Neoplásica da Expressão Gênica / Carcinoma Hepatocelular / MicroRNAs / Neoplasias Hepáticas / Antígenos de Neoplasias Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Moléculas de Adesão Celular / Regulação Neoplásica da Expressão Gênica / Carcinoma Hepatocelular / MicroRNAs / Neoplasias Hepáticas / Antígenos de Neoplasias Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article