Reduced NOV expression correlates with disease progression in colorectal cancer and is associated with survival, invasion and chemoresistance of cancer cells

// Jun Li 1, 2, 3, * , Lin Ye 2, * , Ping-Hui Sun 2 , Fei Zheng 1, 2 , Fiona Ruge 2 , Lucy K. Satherley 2 , Yi Feng 2 , Huishan Zhao 3 , Guifang Du 3 , Tingting Wang 1 , Yao Yang 1 , Xuemei Ma 1 , Shan Cheng 3 , Xiaomei Yang 3 , Hefen Yu 3 , Xu Teng 3 , Yang Si 3 , Zhongtao Zhang 1 , Wen G. Jiang 2, 3 1 Department of General Surgery, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China 2 Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK 3 Cardiff University, Capital Medical University Joint Centre for Biomedical Research and Cancer Institute, Capital Medical University, Beijing, 100069, China * These authors contributed equally to this work Correspondence to: Zhongtao Zhang, email: zhangzht@medmail.com.cn Wen G. Jiang, email: JiangW@cf.ac.uk Keywords: NOV, colorectal cancer, JNK signalling pathways, proliferation, invasion Received: May 06, 2016      Accepted: February 06, 2017      Published: February 17, 2017 ABSTRACT Aberrant expression of nephroblastoma overexpressed (NOV) has been evident in certain malignancies. In the current study, we aim to investigate the role played by NOV in colorectal cancer (CRC). NOV expression was determined in a cohort of 359 CRC tissues and 174 normal colorectal tissues. Its impact on CRC cells was investigated using in vitro NOV knockdown and overexpression models. NOV transcripts were reduced in the CRC tumours compared with the paired adjacent normal colorectal tissues ( p < 0.01) and was associated with distant metastases. NOV knockdown resulted in increased cell proliferation and invasion of RKO cells, whilst an opposite effect was seen in the HT115 NOV over expressing cells. A positive association between Caspase-3/-8 and NOV was seen in NOV knockdown and overexpression cell lines which contributed to the survival of serum deprived CRC cells. Further investigation showed that NOV regulated proliferation, survival and invasion through the JNK pathway. NOV knockdown in RKO cells reduced the responsiveness to 5-Fluorouracil treatment, whilst overexpression in HT115 cells exhibited a contrasting effect. Taken together, NOV is reduced in CRC tumours and this is associated with disease progression. NOV inhibits the proliferation and invasion of CRC cells in vitro . Inhibition of proliferation is mediated by a regulation of Caspase-3/-8, via the JNK pathway, which has potential for predicting and preventing chemoresistance.