The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer

Recently, the long non-coding RNA (lncRNA) H19 has been identified as an oncogenic gene in multiple cancer types and elevated expression of H19 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in colorectal cance...

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Published inOncotarget Vol. 6; no. 26; pp. 22513 - 22525
Main Authors Liang, Wei-Cheng, Fu, Wei-Ming, Wong, Cheuk-Wa, Wang, Yan, Wang, Wei-Mao, Hu, Guo-Xin, Zhang, Li, Xiao, Li-Jia, Wan, David Chi-Cheong, Zhang, Jin-Fang, Waye, Mary Miu-Yee
Format Journal Article
LanguageEnglish
Published United States Impact Journals LLC 08.09.2015
Subjects
Animals
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Epithelial-Mesenchymal Transition - genetics
HCT116 Cells
HEK293 Cells
Heterografts
HT29 Cells
Humans
Mice
Mice, Nude
MicroRNAs - genetics
MicroRNAs - metabolism
Research Paper
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Up-Regulation
ceRNA
lncRNA
miRNA sponges
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Summary:Recently, the long non-coding RNA (lncRNA) H19 has been identified as an oncogenic gene in multiple cancer types and elevated expression of H19 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in colorectal cancer (CRC) especially during epithelial to mesenchymal transition (EMT) progression. In our studies, H19 was characterized as a novel regulator of EMT in CRC. We found that H19 was highly expressed in mesenchymal-like cancer cells and primary CRC tissues. Stable expression of H19 significantly promotes EMT progression and accelerates in vivo and in vitro tumor growth. Furthermore, by using bioinformatics study and RNA immunoprecipitation combined with luciferase reporter assays, we demonstrated that H19 functioned as a competing endogenous RNA (ceRNA) for miR-138 and miR-200a, antagonized their functions and led to the de-repression of their endogenous targets Vimentin, ZEB1, and ZEB2, all of which were core marker genes for mesenchymal cells. Taken together, these observations imply that the lncRNA H19 modulated the expression of multiple genes involved in EMT by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and EMT progression.
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ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.4154