miR-409-3p/-5p promotes tumorigenesis, epithelial-to-mesenchymal transition, and bone metastasis of human prostate cancer.

Abstract

PURPOSE:

miR-409-3p/-5p is a miRNA expressed by embryonic stem cells, and its role in cancer biology and metastasis is unknown. Our pilot studies demonstrated elevated miR-409-3p/-5p expression in human prostate cancer bone metastatic cell lines; therefore, we defined the biologic impact of manipulation of miR-409-3p/-5p on prostate cancer progression and correlated the levels of its expression with clinical human prostate cancer bone metastatic specimens.

EXPERIMENTAL DESIGN:

miRNA profiling of a prostate cancer bone metastatic epithelial-to-mesenchymal transition (EMT) cell line model was performed. A Gleason score human tissue array was probed for validation of specific miRNAs. In addition, genetic manipulation of miR-409-3p/-5p was performed to determine its role in tumor growth, EMT, and bone metastasis in mouse models.

RESULTS:

Elevated expression of miR-409-3p/-5p was observed in bone metastatic prostate cancer cell lines and human prostate cancer tissues with higher Gleason scores. Elevated miR-409-3p expression levels correlated with progression-free survival of patients with prostate cancer. Orthotopic delivery of miR-409-3p/-5p in the murine prostate gland induced tumors where the tumors expressed EMT and stemness markers. Intracardiac inoculation (to mimic systemic dissemination) of miR-409-5p inhibitor-treated bone metastatic ARCaPM prostate cancer cells in mice led to decreased bone metastasis and increased survival compared with control vehicle-treated cells.

CONCLUSION:

miR-409-3p/-5p plays an important role in prostate cancer biology by facilitating tumor growth, EMT, and bone metastasis. This finding bears particular translational importance as miR-409-3p/-5p appears to be an attractive biomarker and/or possibly a therapeutic target to treat bone metastatic prostate cancer.

• Authors: Sajni Josson, Murali Gururajan, Peizhen Hu, Chen Shao, GinaChia-Yi Chu, Haiyen E Zhau, Chunyan Liu, Kaiqin Lao, Chia-Lun Lu, Yi-Tsung Lu, Jake Lichterman, Srinivas Nandana, Quanlin Li, Andre Rogatko, Dror Berel, Edwin M Posadas, Ladan Fazli, Dhruv Sareen, Leland W K Chung
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 17 Pg. 4636-46 (Sep 01 2014) ISSN: 1557-3265 [Electronic] United States
• PMID: 24963047 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• MIRN409 microRNA, human
• MicroRNAs

Topics

• Animals
• Bone Neoplasms (genetics, pathology, secondary)
• Carcinogenesis (genetics)
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice
• MicroRNAs (biosynthesis, genetics)
• Prostatic Neoplasms