IJCEP Copyright © 2007-All rights reserved.
Int J Clin Exp Pathol 2013;6(12):2651-2667

Original Article
Effects and interactions of MiR-577 and TSGA10 in regulating esophageal squamous cell
carcinoma

Xiang Yuan, Jiangtu He, Fenyong Sun, Jiang Gu

Department of Pathology, School of Basic Medical Science, Peking University, Beijing 100083, China; Molecular Pathology Laboratory and
Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou
515041, China; Department of Clinical Laboratory Medicine, Shanghai Tenth People’s Hospital of Tongji University, Shanghai 200072, China;
Department of Central Laboratory, Shanghai Tenth People’s Hospital of Tongji University, Shanghai 200072, China

Received September 26, 2013; Accepted October 29, 2013; Epub November 15, 2013; Published December 1, 2013

Abstract: Testis specific 10 (TSGA10) was originally identified as a testis-specific protein and tumor-associated antigen in a number of cancer
types. In this study, we found that down-regulation of TSGA10 was associated with increased malignancy and clinical features of esophageal
squamous cell carcinomas (ESCCs). Moreover, increased expression of TSGA10 inhibited, while its knockdown promoted, tumor formation in
vivo in nude mice. At the 3’UTR of the TSGA10 gene we identified two binding sites for microRNA-577 (miR-577). Further investigation
demonstrated that expression levels of miR-577 and TSGA10 were negatively correlated to each other in ESCC cell lines and tumor samples.
Moreover, manipulation of miR-577 and TSGA10 expression confirmed that miR-577 can regulate TSGA10 and in turn affect cell proliferation in
vitro. Additionally, with flow cytometry and manipulation of the mir-577/TSGA10 axis, it was found that mir-577/TSGA10 axis influenced the
growth of ESCC through regulating the G1-S phase transition. We also obtained evidence to establish that mir-577/TSGA10 axis activation was
always accompanied by inactivation of the p53 pathway or the Rb pathway or both, thus, the latter two pathways are obligatory for progression of
ESCCs with mir-577/TSGA10 axis activation. In addition, we found that such an interactive pathway in regulating cancer cell proliferation was
restricted to a few cancer types including ESCC, but not uniformly applicable to other cancer types. This newly discovered regulatory
mechanism provides a new dimension for ESCC diagnosis and therapy. (IJCEP1309068).

Keywords: ESCC, TSGA10, miR-577, G1-S phase transition, p53/p21 pathway, Rb/p16 pathway

Address correspondence to: Dr. Jiang Gu, Molecular Pathology Laboratory and Guangdong Provincial Key Laboratory of Infectious Diseases
and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, China. Tel: 86-13502752606; Fax: 86-754-8895 0293;
E-mail: gujiangmd@126.com; jguemailbox@gmail.com; Dr. Fenyong Sun, Department of Clinical Laboratory Medicine, Shanghai Tenth People’
s Hospital of Tongji University, Shanghai 200072, China. Tel: 86-21-66300588; Fax: 86-21-66300588; E-mail: fenyongsunijcep@126.com; Dr.
Xiang Yuan, Department of Pathology, School of Basic Medical Science, Peking University, Beijing 100083, China. E-mail: yuanxiang1105@126.
com