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.
Funding source: Guangdong Natural Science Foundation, Guangdong, China
Award Identifier / Grant number: S2013030013315, 2016A030313083, and 2018A030313544
Funding source: Science and Technology Program of Guangzhou, Guangdong, China
Award Identifier / Grant number: 201607010175, 201707010263, and 201804010066
Funding statement: The authors would like to thank members of the Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes for providing discussion and support throughout the present study. The present study was supported by grants from the Guangdong Natural Science Foundation, Guangdong, China (Funder Id: 10.13039/501100003453, grant nos.: S2013030013315, 2016A030313083, and 2018A030313544) and the Science and Technology Program of Guangzhou, Guangdong, China (grant nos.: 201607010175, 201707010263, and 201804010066).
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