lncRNA H19/miR‐675 axis represses prostate cancer metastasis by targeting TGFBI

Prostate cancer is a leading cause of cancer‐related mortality in men worldwide and there is a lack of effective treatment options for advanced (metastatic) prostate cancer. Currently, limited knowledge is available concerning the role of long non‐coding RNAs in prostate cancer metastasis. In this s...

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Bibliographic Details
Published in:The FEBS journal 2014-08, Vol.281 (16), p.3766-3775
Main Authors: Zhu, Miaojun, Chen, Qin, Liu, Xin, Sun, Qian, Zhao, Xian, Deng, Rong, Wang, Yanli, Huang, Jian, Xu, Ming, Yan, Jianshe, Yu, Jianxiu
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Base Sequence
Binding Sites
Bone Neoplasms - genetics
Bone Neoplasms - metabolism
Bone Neoplasms - secondary
Cell adhesion & migration
Cell Line, Tumor
Cell Movement
Epithelial Cells - physiology
Extracellular Matrix Proteins - genetics
Extracellular Matrix Proteins - metabolism
Gene Expression Regulation, Neoplastic
Humans
lncRNA H19
Male
Medical research
Metastasis
MicroRNAs - genetics
miR‐675
Prostate - pathology
Prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Ribonucleic acid
RNA
RNA Interference
RNA, Long Noncoding - genetics
RNA, Messenger - genetics
TGFBI
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - metabolism
tumor metastasis
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Summary:Prostate cancer is a leading cause of cancer‐related mortality in men worldwide and there is a lack of effective treatment options for advanced (metastatic) prostate cancer. Currently, limited knowledge is available concerning the role of long non‐coding RNAs in prostate cancer metastasis. In this study, we found that long non‐coding RNA H19 (H19) and H19‐derived microRNA‐675 (miR‐675) were significantly downregulated in the metastatic prostate cancer cell line M12 compared with the non‐metastatic prostate epithelial cell line P69. Upregulation of H19 in P69 and PC3 cells significantly increased the level of miR‐675 and repressed cell migration; however, ectopic expression of H19 in M12 cells could not increase the level of miR‐675 and therefore had no effect on cell migration. Furthermore, we found that the expression level of either H19 or miR‐675 in P69 cells was negatively associated with the expression of transforming growth factor β induced protein (TGFBI), an extracellular matrix protein involved in cancer metastasis. Dual luciferase reporter assays showed that miR‐675 directly bound with 3′UTR of TGFBI mRNA to repress its translation. Taken together, we show for the first time that the H19–miR‐675 axis acts as a suppressor of prostate cancer metastasis, which may have possible diagnostic and therapeutic potential for advanced prostate cancer. In this study, we show long non‐coding RNA H19 represses prostate cancer metastasis in a miR‐675‐dependent manner. We further identify miR‐675 directly inhibits the expression of an ECM protein TGFBI, which is involved in migration of cancer cells. Our findings provide a novel understanding of the roles of H19/miR‐675 in prostate cancer metastasis and the mechanisms involved.
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.12902