The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer
Wei-Cheng Liang,Weiming Fu,Cheuk Wa Wong,Yan Wang,Wei Mao Wang,Guo Xin Hu,Li Zhang,Li Jia Xiao,David Chi Cheong Wan,Jinfang Zhang,Mary M.Y. Waye +10 more
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TLDR
It is implied 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.Abstract:
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.read more
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CA : A Cancer Journal for Clinicians
Patrizia Agostinis,Kristian Berg,Keith A. Cengel,Thomas H. Foster,Albert W. Girotti,Sandra O. Gollnick,Stephen M. Hahn,Michael R. Hamblin,Asta Juzeniene,David Kessel,Mladen Korbelik,Johan Moan,Pawel Mroz,Dominika Nowis,Jacques Piette,Brian C. Wilson,Jakub Golab +16 more
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ceRNA in cancer: possible functions and clinical implications
TL;DR: The mechanisms and molecular bases of ceRNA networks are introduced, their roles in the pathogenesis of cancer as well as methods of predicting and validating ceRNA interplay are discussed and the possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets are envisioned.
Journal ArticleDOI
Noncoding RNA:RNA Regulatory Networks in Cancer.
Jia Jia Chan,Yvonne Tay +1 more
TL;DR: Recent integrative analyses have provided evidence that new computational platforms and experimental approaches can be harnessed together to distinguish key ceRNA interactions in specific cancers, which could facilitate the identification of robust biomarkers and therapeutic targets, and hence, more effective cancer therapies and better patient outcome and survival.
Journal ArticleDOI
The H19 Long non-coding RNA in cancer initiation, progression and metastasis – a proposed unifying theory
TL;DR: The growing evidence of H19’s involvement in both proliferation and differentiation processes, together with its involvement in epithelial to mesenchymal transition (EMT), has led to the conclusion that some of the recent disputes and discrepancies arising from current research findings can be resolved from a viewpoint supporting the oncogenic properties of H 19.
Journal ArticleDOI
Carcinoma-associated fibroblasts promote the stemness and chemoresistance of colorectal cancer by transferring exosomal lncRNA H19
Jing Ren,Liang Ding,Dongya Zhang,Guoping Shi,Qianyun Xu,Sunan Shen,Yaping Wang,Tingting Wang,Yayi Hou +8 more
TL;DR: It is indicated that H19 expressed by CAFs of the colorectal tumor stroma contributes to tumor development and chemoresistance and up-regulation of H19 was confirmed in CRC patient samples at different tumor node metastasis (TNM) stages.
References
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A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?
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CA : A Cancer Journal for Clinicians
Patrizia Agostinis,Kristian Berg,Keith A. Cengel,Thomas H. Foster,Albert W. Girotti,Sandra O. Gollnick,Stephen M. Hahn,Michael R. Hamblin,Asta Juzeniene,David Kessel,Mladen Korbelik,Johan Moan,Pawel Mroz,Dominika Nowis,Jacques Piette,Brian C. Wilson,Jakub Golab +16 more