Biomaterial Database

KH-type splicing regulatory protein is involved in esophageal squamous cell carcinoma progression. 2017

Yuji Fujita, and Kiyoshi Masuda, and Junichi Hamada, and Katsutoshi Shoda, and Takuya Naruto, and Satoshi Hamada, and Yuko Miyakami, and Tomohiro Kohmoto, and Miki Watanabe, and Rizu Takahashi, and Shoichiro Tange, and Masako Saito, and Yasusei Kudo, and Hitoshi Fujiwara, and Daisuke Ichikawa, and Akira Tangoku, and Eigo Otsuji, and Issei Imoto

Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

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.