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The miR-124-Prolyl Hydroxylase P4HA1-MMP1 axis plays a critical role in prostate cancer progression

Overview of attention for article published in Oncotarget, July 2014
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Title
The miR-124-Prolyl Hydroxylase P4HA1-MMP1 axis plays a critical role in prostate cancer progression
Published in
Oncotarget, July 2014
DOI 10.18632/oncotarget.2208
Pubmed ID
Authors

Balabhadrapatruni V. S. K. Chakravarthi, Satya S. Pathi, Moloy T. Goswami, Marcin Cieślik, Heng Zheng, Sivakumar Nallasivam, Subramanyeswara R. Arekapudi, Xiaojun Jing, Javed Siddiqui, Jyoti Athanikar, Shannon L. Carskadon, Robert J. Lonigro, Lakshmi P. Kunju, Arul M. Chinnaiyan, Nallasivam Palanisamy, Sooryanarayana Varambally

Abstract

Collagen prolyl hydroxylases (C-P4HAs) are a family of enzymes involved in collagen biogenesis. One of the isoforms of P4HA, Prolyl 4-hydroxylase, alpha polypeptide I (P4HA1), catalyzes the formation of 4-hydroxyproline that is essential for the proper three-dimensional folding of newly synthesized procollagen chains. Here, we show the overexpression of P4HA1 in aggressive prostate cancer. Immunohistochemical analysis using tissue microarray demonstrated that P4HA1 expression was correlated with prostate cancer progression. Using in vitro studies, we showed that P4HA1 plays a critical role in prostate cancer cell growth and tumor progression. Expression profiling studies using P4HA1 modulated prostate cells suggested regulation of Matrix metalloproteases 1. The invasive properties of P4HA1 overexpressing cells were reversed by blocking MMP1. Our studies indicate P4HA1 copy number gain in a subset of metastatic prostate tumors and its expression is also regulated by microRNA-124. MiR-124 in turn is negatively regulated by transcriptional repressors EZH2 and CtBP1, both of which are overexpressed in aggressive prostate cancer. Chick chorioallantoic membrane (CAM) assay and mice xenograft investigations show that P4HA1 is required for tumor growth and metastasis in vivo. Our observations suggest that P4HA1 plays a critical role in prostate cancer progression and could serve as a viable therapeutic target.

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 6 21%
Professor > Associate Professor 5 17%
Student > Ph. D. Student 5 17%
Researcher 4 14%
Student > Master 3 10%
Other 3 10%
Unknown 3 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 31%
Agricultural and Biological Sciences 6 21%
Medicine and Dentistry 5 17%
Mathematics 1 3%
Environmental Science 1 3%
Other 1 3%
Unknown 6 21%