Loss of ZG16 is regulated by miR-196a and contributes to stemness and progression of colorectal cancer

// Xiaobing Chen 1, * , Peng Du 2, * , Junjun She 3, * , Liang Cao 1, * , Yingchao Li 4 , Hongping Xia 3 1 Department of Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China 2 Department of Colorectal Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China 3 Department of General Surgery, The First Affiliated Hospital of Xi’An Jiaotong University, Xi’An 710061, China 4 Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China * These authors have contributed equally to this work Correspondence to: Xiaobing Chen, email: 2290773710@qq.com Junjun She, email: sjuns@sina.com Hongping Xia, email: xiahp82@gmail.com Keywords: ZG16, Colorectal cancer, LGR5, stemness, miR-196a Received: August 15, 2016     Accepted: October 31, 2016     Published: November 17, 2016 ABSTRACT Colorectal cancer (CRC) is one of the most common malignant tumour and the leading cause of cancer-related mortality worldwide. Clarification of the mechanism that underlies CRC tumorigenesis and progression therefore is urgently needed ffor developing novel therapies. Through analysis of The Cancer Genome Atlas (TCGA) dataset, we identified an interesting gene, ZG16, which is significantly decreased in CRC samples compared to adjacent non-tumor tissues and associated with prognosis of patients. We found that the expression of ZG16 correlated with CRC related genes which were regulated by APC/CTNNB1 pathway. Interestingly, the expression of ZG16 was negatively correlated with CRC stem cell marker, LGR5. Overexpression of ZG16 significantly inhibits growth and sphere formation of stem-like CRC cells. Moreover, we also identified an upstream regulator of ZG16, miR-196a, which was significantly overexpressed in CRC and promotes cell growth and stemness. In conclusion, this study demonstrated that loss of ZG16 is regulated by miR-196a and contributes to stemness and progression of CRC, which may provide a promising therapeutic strategy for advanced CRCs.