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Cancers 2018, 10(8), 273; https://doi.org/10.3390/cancers10080273

Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer

1
Department of Biochemistry and Convergence Medical Sciences and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, Korea
2
Department of Bioindustry and Bioresource Engineering, College of Life Sciences, Sejong University, Seoul 05006, Korea
*
Author to whom correspondence should be addressed.
Received: 12 July 2018 / Revised: 2 August 2018 / Accepted: 15 August 2018 / Published: 16 August 2018
(This article belongs to the Special Issue Targeting Raf Kinase Inhibitor Protein (RKIP) in Cancer)
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Abstract

Raf kinase inhibitor protein (RKIP) plays a critical role in many signaling pathways as a multi-functional adapter protein. In particular, the loss of RKIP’s function in certain types of cancer cells results in epithelial to mesenchymal transition (EMT) and the promotion of cancer metastasis. In addition, RKIP inhibits autophagy by modulating LC3-lipidation and mTORC1. How the RKIP-dependent inhibition of autophagy is linked to EMT and cancer progression is still under investigation. In this study, we investigated the ways by which RKIP interacts with key gene products in EMT and autophagy during the progression of prostate cancer. We first identified the gene products of interest using the corresponding gene ontology terms. The weighted-gene co-expression network analysis (WGCNA) was applied on a gene expression dataset from three groups of prostate tissues; benign prostate hyperplasia, primary and metastatic cancer. We found two modules of highly co-expressed genes, which were preserved in other independent datasets of prostate cancer tissues. RKIP showed potentially novel interactions with one EMT and seven autophagy gene products (TGFBR1; PIK3C3, PIK3CB, TBC1D25, TBC1D5, TOLLIP, WDR45 and WIPI1). In addition, we identified several upstream transcription modulators that could regulate the expression of these gene products. Finally, we verified some RKIP novel interactions by co-localization using the confocal microscopy analysis in a prostate cancer cell line. To summarize, RKIP interacts with EMT and autophagy as part of the same functional unit in developing prostate cancer. View Full-Text
Keywords: RKIP; PEBP1; autophagy; EMT; cancer; microarrays; TCGA; WGCNA RKIP; PEBP1; autophagy; EMT; cancer; microarrays; TCGA; WGCNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Ahmed, M.; Lai, T.H.; Zada, S.; Hwang, J.S.; Pham, T.M.; Yun, M.; Kim, D.R. Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer. Cancers 2018, 10, 273.

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