Cargando…

Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma

MicroRNA-9 (miR-9) dysregulation is implicated in a variety of human malignancies including hepatocellular carcinoma (HCC), but its role remains contradictory. In this study, we explored the expression and methylation status of miR-9 in HCC samples, as well as the tumor-related functions of miR-9 in...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Jiangbo, Cheng, Jin, Zeng, Zhenzhen, Wang, Yongfeng, Li, Xiaojun, Xie, Qing, Jia, Junqiao, Yan, Ying, Guo, Zhengyang, Gao, Jian, Yao, Mingjie, Chen, Xiangmei, Lu, Fengmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747208/
https://www.ncbi.nlm.nih.gov/pubmed/26547929
_version_ 1782414937320062976
author Zhang, Jiangbo
Cheng, Jin
Zeng, Zhenzhen
Wang, Yongfeng
Li, Xiaojun
Xie, Qing
Jia, Junqiao
Yan, Ying
Guo, Zhengyang
Gao, Jian
Yao, Mingjie
Chen, Xiangmei
Lu, Fengmin
author_facet Zhang, Jiangbo
Cheng, Jin
Zeng, Zhenzhen
Wang, Yongfeng
Li, Xiaojun
Xie, Qing
Jia, Junqiao
Yan, Ying
Guo, Zhengyang
Gao, Jian
Yao, Mingjie
Chen, Xiangmei
Lu, Fengmin
author_sort Zhang, Jiangbo
collection PubMed
description MicroRNA-9 (miR-9) dysregulation is implicated in a variety of human malignancies including hepatocellular carcinoma (HCC), but its role remains contradictory. In this study, we explored the expression and methylation status of miR-9 in HCC samples, as well as the tumor-related functions of miR-9 in vitro. Bioinformatics analysis, array-based RNA expression profile, and literature retrieval were used to identify miR-9 targets in HCC. The potential downstream candidates were then validated by luciferase reporter assay, real-time quantitative PCR, and western blot or enzyme linked immunosorbent assay (ELISA). The expression status and clinicopathologic significances of miR-9 target genes in clinical samples were further explored. The results showed that miR-9 was frequently downregulated in primary HCC. Its silencing was largely contributed by a high frequency (42.5%) of mir-9-1 hypermethylation, which was correlated with bigger tumor size (P = 0.0234). In vitro functional studies revealed that miR-9 restoration retarded HCC cell proliferation and migration. IL-6, AP3B1, TC10, ONECUT2, IGF2BP1, MYO1D, and ANXA2 were confirmed to be miR-9 targets in HCC. Among them, ONECUT2, IGF2BP1, and ANXA2 were confirmed to be aberrantly upregulated in HCC. Moreover, upregulation of ONECUT2, IGF2BP1, and IL-6 were significantly associated with poor post-surgery prognosis (P = 0.0458, P = 0.0037 and P = 0.0461, respectively). Mechanically, miR-9 plays a tumor suppressive role partially through a functional miR-9/IGF2BP1/AKT&ERK axis. Our study suggests that miR-9 functions as a tumor suppressor in HCC progression by inhibiting a series of target genes, including the newly validated miR-9/IGF2BP1/AKT&ERK axis, thus providing potential therapeutic targets and novel prognostic biomarkers for HCC patients.
format Online
Article
Text
id pubmed-4747208
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-47472082016-03-25 Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma Zhang, Jiangbo Cheng, Jin Zeng, Zhenzhen Wang, Yongfeng Li, Xiaojun Xie, Qing Jia, Junqiao Yan, Ying Guo, Zhengyang Gao, Jian Yao, Mingjie Chen, Xiangmei Lu, Fengmin Oncotarget Research Paper MicroRNA-9 (miR-9) dysregulation is implicated in a variety of human malignancies including hepatocellular carcinoma (HCC), but its role remains contradictory. In this study, we explored the expression and methylation status of miR-9 in HCC samples, as well as the tumor-related functions of miR-9 in vitro. Bioinformatics analysis, array-based RNA expression profile, and literature retrieval were used to identify miR-9 targets in HCC. The potential downstream candidates were then validated by luciferase reporter assay, real-time quantitative PCR, and western blot or enzyme linked immunosorbent assay (ELISA). The expression status and clinicopathologic significances of miR-9 target genes in clinical samples were further explored. The results showed that miR-9 was frequently downregulated in primary HCC. Its silencing was largely contributed by a high frequency (42.5%) of mir-9-1 hypermethylation, which was correlated with bigger tumor size (P = 0.0234). In vitro functional studies revealed that miR-9 restoration retarded HCC cell proliferation and migration. IL-6, AP3B1, TC10, ONECUT2, IGF2BP1, MYO1D, and ANXA2 were confirmed to be miR-9 targets in HCC. Among them, ONECUT2, IGF2BP1, and ANXA2 were confirmed to be aberrantly upregulated in HCC. Moreover, upregulation of ONECUT2, IGF2BP1, and IL-6 were significantly associated with poor post-surgery prognosis (P = 0.0458, P = 0.0037 and P = 0.0461, respectively). Mechanically, miR-9 plays a tumor suppressive role partially through a functional miR-9/IGF2BP1/AKT&ERK axis. Our study suggests that miR-9 functions as a tumor suppressor in HCC progression by inhibiting a series of target genes, including the newly validated miR-9/IGF2BP1/AKT&ERK axis, thus providing potential therapeutic targets and novel prognostic biomarkers for HCC patients. Impact Journals LLC 2015-10-19 /pmc/articles/PMC4747208/ /pubmed/26547929 Text en Copyright: © 2015 Zhang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Jiangbo
Cheng, Jin
Zeng, Zhenzhen
Wang, Yongfeng
Li, Xiaojun
Xie, Qing
Jia, Junqiao
Yan, Ying
Guo, Zhengyang
Gao, Jian
Yao, Mingjie
Chen, Xiangmei
Lu, Fengmin
Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma
title Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma
title_full Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma
title_fullStr Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma
title_full_unstemmed Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma
title_short Comprehensive profiling of novel microRNA-9 targets and a tumor suppressor role of microRNA-9 via targeting IGF2BP1 in hepatocellular carcinoma
title_sort comprehensive profiling of novel microrna-9 targets and a tumor suppressor role of microrna-9 via targeting igf2bp1 in hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747208/
https://www.ncbi.nlm.nih.gov/pubmed/26547929
work_keys_str_mv AT zhangjiangbo comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT chengjin comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT zengzhenzhen comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT wangyongfeng comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT lixiaojun comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT xieqing comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT jiajunqiao comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT yanying comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT guozhengyang comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT gaojian comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT yaomingjie comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT chenxiangmei comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma
AT lufengmin comprehensiveprofilingofnovelmicrorna9targetsandatumorsuppressorroleofmicrorna9viatargetingigf2bp1inhepatocellularcarcinoma