Int J Biol Sci 2020; 16(4):719-729. doi:10.7150/ijbs.41125

Research Paper

CHIP-mediated ubiquitination of Galectin-1 predicts colorectal cancer prognosis

Weimin Wang1,2,3, Zhen Zhou1,3, Liangliang Xiang1,3, Mengying Lv1,3, Tengyang Ni1,3, Jianliang Deng2, Haibo Wang1,3, Sunagawa Masatara4, Yan Zhou1,2,3✉, Yanqing Liu1,2,3✉

1. Institute of Traslational Medicine, Medical College, Yangzhou University, Yangzhou 225001, PR China
2. Department of Oncology, Yixing Hospital Affiliated to Medical College of Yangzhou University, Yixing, Jiangsu, 214200, PR China
3. The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, 225001, PR China
4. Department of Physiology, School of Medicine, Showa University, Tokyo 142, Japan

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Citation:
Wang W, Zhou Z, Xiang L, Lv M, Ni T, Deng J, Wang H, Masatara S, Zhou Y, Liu Y. CHIP-mediated ubiquitination of Galectin-1 predicts colorectal cancer prognosis. Int J Biol Sci 2020; 16(4):719-729. doi:10.7150/ijbs.41125. Available from http://www.ijbs.com/v16p0719.htm

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Abstract

CHIP and Galectin-1 are associated with the development of metastasis in cancer. However, the precise roles of CHIP or Gal1 in colorectal cancer are uncertain. Here, our study explored the relationship and clinical significance of CHIP or Gal1 in CRC. CHIP or Gal1 expression was significantly decreased or up-regulated in CRC compared with adjacent noncancerous tissues by immunohistochemistry on a CRC tissue microarray, respectively. Low CHIP or high Gal1 expression significantly correlated with clinicopathological characteristics in patients, as well as with shorter overall survival. Multivariate Cox regression analysis revealed that CHIP or Gal1 expression was an independent prognostic factor for CRC patients. Moreover, CHIP associated with Gal1 has a synergistic effect on the prediction of CRC prognosis. In vitro and vivo, high CHIP or low Gal1 expression inhibit CRC growth or metastasis. Our results found that CHIP could degradate Gal1 by ubiquitination. In summary, CHIP could inhibit CRC growth or metastasis through promoting Gal1 ubiquitination and degradation by proteasome. CHIP and Gal1 expressions are novel candidate prognostic markers in CRC. A combined effect of CHIP and Gal1 as efficient prognostic indicators was found for the first time.

Keywords: CRC, CHIP, Gal1, prognosis, ubiquitination, metastasis