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

Li, Jun, Ye, Lin, Sun, Ping-Hui, Zheng, Fei, Ruge, Fiona, Satherley, Lucy, Feng, Yi, Zhao, Huishan, Du, Guifang, Wang, Tingting, Yang, Yao, Ma, Xuemei, Cheng, Shan, Yang, Xiaomei, Yu, Hefen, Teng, Xu, Si, Yang, Zhang, Zhongtao and Jiang, Wen 2017. Reduced NOV expression correlates with disease progression in colorectal cancer and is associated with survival, invasion and chemoresistance of cancer cells. Oncotarget 10.18632/oncotarget.15439

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: NOV, colorectal cancer, JNK signalling pathways, proliferation, invasion
Publisher: Impact Journals
ISSN: 1949-2553
Funders: the National Key Clinical Specialist construction Programs of China, Cancer Research Wales, the Chinese Medical Research Scholarship of Cardiff University
Date of First Compliant Deposit: 21 February 2017
Date of Acceptance: 6 February 2017
Last Modified: 25 Jun 2019 20:44
URI: http://orca-mwe.cf.ac.uk/id/eprint/98180

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