title: High expression of fibronectin is associated with poor prognosis, cell proliferation and malignancy via the NF-κB/p53-apoptosis signaling pathway in colorectal cancer.
abstract: Fibronectin is a glycoprotein of the extracellular matrix, and regulates the processes of self-renewal and cell cycle progression. This study aimed to investigate fibronectin expression in colorectal cancer (CRC) and elucidate the effects of fibronectin on CRC by using a knockdown approach. Immunohistochemistry was used to evaluate the expression of fibronectin in 107 CRC patient tissues and gene expression was detected by real-time quantitative PCR (qPCR) and western blot analysis. Based on the above findings, the association among fibronectin expression, clinicopathological features and prognosis was analyzed. Next, fibronectin expression was silenced by small-interfering RNAs (siRNAs) and the effects of fibronectin siRNA transfection on CRC cells and tumor growth in nude mice were assessed. Expression of genes in the NF-κB/p53-apoptosis signaling pathway were analyzed after fibronectin siRNA transfection both in vitro and in vivo. Based on the results, high expression of fibronectin was observed both in the CRC tissues and CRC cell lines. The expression level was positively correlated with TNM stage (P=0.0025) and distant metastasis (P=0.0013). By Kaplan-Meier analysis, the patients with low fibronectin expression had a longer survival time comparing to those with relatively high expression. Knockdown of fibronectin suppressed SW480 cell proliferation, migration and invasion. In addition, knockdown of fibronectin led to S phase cell cycle arrest. The following study showed that the NF-κB/p53-apoptosis signaling pathway in CRC was affected by fibronectin knockdown. Tumor formation was also depressed by fibronectin siRNA transfection of CRC cells. These results showed the significant role of fibronectin in CRC tissues and cell lines. Therefore, fibronectin may be regarded as a potential target for CRC treatment.
authors.affiliation: Medical Imaging Center, First People's Hospital of Huaihua City, Huaihua, Hunan 418000, P.R. China.
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Yi
authors.affiliation: Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Enhua
authors.initials: E
authors.lastname: Xiao
authors.affiliation: Medical Imaging Center, First People's Hospital of Huaihua City, Huaihua, Hunan 418000, P.R. China.
authors.forename: Ru
authors.initials: R
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, First People's Hospital of Huaihua City, Huaihua, Hunan 418000, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Luo
authors.affiliation: Medical Imaging Center, First People's Hospital of Huaihua City, Huaihua, Hunan 418000, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009368:Neoplasm Transplantation; D011379:Prognosis; D059807:S Phase Cell Cycle Checkpoints; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005353:Fibronectins; D016328:NF-kappa B; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53