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ID 110988
Author
Fujita, Yuji Tokushima University|Kyoto Prefectural University of Medicine
Hamada, Junichi Tokushima University|Kyoto Prefectural University of Medicine
Shoda, Katsutoshi Tokushima University|Kyoto Prefectural University of Medicine
Hamada, Satoshi Tokushima University
Miyakami, Yuko Tokushima University
Kohmoto, Tomohiro Tokushima University
Watanabe, Miki Tokushima University
Takahashi, Rizu Tokushima University
Fujiwara, Hitoshi Kyoto Prefectural University of Medicine
Ichikawa, Daisuke Kyoto Prefectural University of Medicine|University of Yamanashi
Otsuji, Eigo Kyoto Prefectural University of Medicine
Keywords
KHSRP
oncogene
RNA-binding protein
microRNA
esophageal squamous cell carcinoma
Content Type
Journal Article
Description
KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein, which is involved in several post-transcriptional aspects of RNA metabolism, including microRNA (miRNA) biogenesis. It affects distinct cell functions in different tissues and can have an impact on various pathological conditions. In the present study, we investigated the oncogenic functions of KHSRP and their underlying mechanisms in the pathogenesis of esophageal squamous cell carcinoma (ESCC). KHSRP expression levels were elevated in ESCC tumors when compared with those in non-tumorous tissues by immunohistochemistry, and cytoplasmic KHSRP overexpression was found to be an independent prognosticator for worse overall survival in a cohort of 104 patients with ESCC. KHSRP knockdown inhibited growth, migration, and invasion of ESCC cells. KHSRP knockdown also inhibited the maturation of cancer-associated miRNAs, such as miR-21, miR-130b, and miR-301, and induced the expression of their target mRNAs, such as BMP6, PDCD4, and TIMP3, resulting in the inhibition of epithelial-to-mesenchymal transition. Our findings uncover a novel oncogenic function of KHSRP in esophageal tumorigenesis and implicate its use as a marker for prognostic evaluation and as a putative therapeutic target in ESCC.
Journal Title
Oncotarget
ISSN
19492553
Publisher
Impact Journals
Volume
8
Issue
60
Start Page
101130
End Page
101145
Published Date
2017-09-15
Rights
Copyright: Fujita et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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DOI (Published Version)
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language
eng
TextVersion
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departments
Medical Sciences
Oral Sciences