Regulation and related mechanism of GSN mRNA level by hnRNPK in lung adenocarcinoma cells
Author:
Liu Xiao-hui1, Ma Jie1, Feng Jun-xia2, Feng Yuan1, Zhang Yun-fang2, Liu Lang-xia1
Affiliation:
1. Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology , Jinan University , 601 Huangpu Avenue West , Guangzhou 510632 , China 2. Department of Nephrology, Huadu District People’s Hospital of Guangzhou , Southern Medical University , Guangzhou 510800 , China
Abstract
Abstract
Gelsolin (GSN) is an actin filament-capping protein that plays a key role in cell migration. Here we show that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulates GSN expression level by binding to the 3′-untranslated region (3′UTR) of GSN mRNA in non-small cell lung cancers (NSCLC) H1299 cells which are highly metastatic and express high level of GSN. We found that hnRNPK overexpression increased the mRNA and protein level of GSN, whereas hnRNPK knockdown by siRNA decreased the mRNA and protein level of GSN in both H1299 and A549 cells, indicating a positive role of hnRNPK in the regulation of GSN expression. Furthermore, hnRNPK knockdown affected the migration ability of H1299 and A549 cells which could be rescued by ectopic expression of GSN in those cells. Conversely, GSN knockdown in hnRNPK-overexpressing cells could abort the stimulatory effect of hnRNPK on the cell migration. These results suggest that hnRNPK function in the regulation of cell migration is GSN-dependent. Taken together, these data unveiled a new mechanism of regulation of the GSN expression by hnRNPK and provides new clues for the discovery of new anti-metastatic therapy.
Funder
Guangdong Natural Science Foundation, Guangdong, China Science and Technology Program of Guangzhou, Guangdong, China
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
Reference42 articles.
1. Arcaro, A. (1998). The small GTP-binding protein rac promotes the dissociation of gelsolin from actin filaments in neutrophils. J. Biol. Chem. 273, 805–813. 2. Azuma, T., Witke, W., Stossel, T.P., Hartwig, J.H., and Kwiatkowski, D.J. (1998). Gelsolin is a downstream effector of rac for fibroblast motility. EMBO J. 17, 1362–1370. 3. Barboro, P., Repaci, E., Rubagotti, A., Salvi, S., Boccardo, S., Spina, B., Truini, M., Introini, C., Puppo, P., and Ferrari, N. (2009). Heterogeneous nuclear ribonucleoprotein K: altered pattern of expression associated with diagnosis and prognosis of prostate cancer. Br. J. Cancer 100, 1608–1616. 4. Carpenter, B., Mckay, M., Dundas, S.R., Lawrie, L.C., Telfer, C., and Murray, G.I. (2006). Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer. Br. J. Cancer 95, 921–927. 5. Cervero, P., Himmel, M., Kruger, M., and Linder, S. (2012). Proteomic analysis of podosome fractions from macrophages reveals similarities to spreading initiation centres. Eur. J. Cell Biol. 91, 908–922.
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