Data from <i>LINC00869</i> Promotes Hepatocellular Carcinoma Metastasis via Protrusion Formation

Abstract

<div>Abstract<p>Coordination of filament assembly and membrane remodeling is required for the directional migration of cancer cells. The Wiskott–Aldrich syndrome protein (WASP) recruits the actin-related protein (ARP) 2/3 complex to assemble branched actin networks. The goal of our study was to assess the potential regulatory role exerted by the novel long noncoding RNA (lncRNA) <i>LINC00869</i> on hepatocellular carcinoma (HCC) cells. We used HCC cells to overexpress or knockdown <i>LINC00869</i>, analyzed patient data from publicly available databases and Cancer Hospital Affiliated with Zhengzhou University, and used a xenograft mouse model of HCC to study the molecular mechanism associated with <i>LINC00869</i> expression. We found that high levels of <i>LINC00869</i> expression were associated with poor prognosis in patients with HCC. Next, we detected an interaction between <i>LINC00869</i> and both WASP and ARP2 in HCC cells, and observed a modulatory effect of <i>LINC00869</i> on the phosphorylation of WASP at Y291 and the activity of cell division control protein 42 (CDC42). These modulatory roles were required for WASP/CDC42 activity on F-actin polymerization to enhance membrane protrusion formation and maintain persistent cell polarization. This, in turn, promoted the migration and invasion abilities of HCC cells. Finally, we confirmed the role of <i>LINC00869</i><i>in vivo</i>, using the tumor xenograft mouse model; and identified a positive correlation between <i>LINC00869</i> expression levels and the phosphorylation levels of WASP in HCC samples. Overall, our findings suggest a unique mechanism by which <i>LINC00869</i> orchestrates membrane protrusion during migration and invasion of HCC cells.</p>Implications:<p>LncRNA <i>LINC00869</i> regulates the activity of CDC42–WASP pathway and positively affects protrusion formation in HCC cells, which expands the current understanding of lncRNA functions as well as gives a better understanding of carcinogenesis.</p></div>