KH-type splicing regulatory protein is involved in esophageal squamous cell carcinoma progression
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Yuji Fujita1,2,*, Kiyoshi Masuda1,*, Junichi Hamada1,2,*, Katsutoshi Shoda1,2, Takuya Naruto1, Satoshi Hamada1, Yuko Miyakami1, Tomohiro Kohmoto1, Miki Watanabe1, Rizu Takahashi1, Shoichiro Tange1, Masako Saito1, Yasusei Kudo3, Hitoshi Fujiwara2, Daisuke Ichikawa2,4, Akira Tangoku5, Eigo Otsuji2 and Issei Imoto1
1Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
2Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
3Department of Oral Molecular Pathology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
4First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
5Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
*These authors contributed equally to this work
Issei Imoto, email: email@example.com
Keywords: KHSRP, oncogene, RNA-binding protein, microRNA, esophageal squamous cell carcinoma
Received: June 22, 2017 Accepted: August 25, 2017 Published: September 15, 2017
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.
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