Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/110201
Title: | Restoring mir122 in human stem-like hepatocarcinoma cells, prompts tumor dormancy through smad-independent TGF-β pathway. |
Author: | Boix i Ferrero, Loreto López-Oliva, Juan Manuel Rhodes Cabrerizo, Ana Carolina Bruix Tudó, Jordi |
Keywords: | Oncologia Càncer Cèl·lules mare Càncer de fetge Oncology Cancer Stem cells Liver cancer |
Issue Date: | 1-Nov-2016 |
Publisher: | Impact Journals |
Abstract: | miR122 is the prevalent miRNA in adult healthy liver and it is responsible for liver stem cell differentiation towards hepatocyte lineage. Its expression is frequently lost in hepatocellular carcinoma (HCC). We studied the effects of restoring miR122 expression in a distinctive cell line derived from human HCC-BCLC9 cells-with a solid stem-like cell profile, high tumor initiating ability and undetectable miR122 expression. We generated a stable BCLC9 cell line that expresses miR122 (BCLC9-miR122). Restitution of miR122 in BCLC9 cells, decreases cell proliferation rate and reduces significantly tumor size in vivo. BCLC9-miR122 cells down-regulate expression of MYC, KLF4, FOXM1, AKT2 and AKT3 genes and up-regulate FOXO1 and FOXO3A gene expression. In addition, miR122 transfected cells decreased AKT2 kinase activation while decreased FOXO1 and FOXO3A protein inactivation. Reduction in tumor size in BCLC9-miR122 associated with an increase in p38MAPK protein expression and activation leading to a low phospho-ERK1/2 to phospho-p38 ratio. Treatment of miR122 positive cells with an inhibitor of TGFBR1 activation, abolished tumor dormancy program and recovered cell proliferation rate through a Smad-independent TGF-β response.HCC stem-like cells can be directed towards cell differentiation and tumor dormancy by restoring miR122 expression. We demonstrate, for the first time, that dormancy program is achieved through a Smad-independent TGF-β pathway. Restablishing miR122 expression is a promising therapeutic strategy that would work concurrently reducing tumor aggressiveness and decreasing disease recurrence. |
Note: | Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.11885 |
It is part of: | Oncotarget, 2016, vol. 7, num. 44, p. 71309-71329 |
URI: | http://hdl.handle.net/2445/110201 |
Related resource: | https://doi.org/10.18632/oncotarget.11885 |
ISSN: | 1949-2553 |
Appears in Collections: | Articles publicats en revistes (Medicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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