posted on 2024-03-01, 13:00authored byXiaowen Shao, Yamei Dang, Tingting Zhang, Nan Bai, Jianing Huang, Mengya Guo, Li Sun, Minghe Li, Xiao Sun, Xinran Zhang, Feng Han, Ning Zhang, Hao Zhuang, Yongmei Li
Summary of the sequencing coverage and quality statistics of the RIP-Seq analysis.
Funding
National Natural Science Foundation of China (NSFC)
National Science and Technology Major Project (国家科技重大专项)
Henan Provincial Science and Technology Research Project (河南省科技攻关项目)
Health Commission of Henan Province (河南省卫生健康委员会)
Tianjin Municipal Education Commission (天津市教育委员会)
Tianjin First Central Hospital Science and Technology
History
ARTICLE ABSTRACT
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) LINC00869 on hepatocellular carcinoma (HCC) cells. We used HCC cells to overexpress or knockdown LINC00869, 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 LINC00869 expression. We found that high levels of LINC00869 expression were associated with poor prognosis in patients with HCC. Next, we detected an interaction between LINC00869 and both WASP and ARP2 in HCC cells, and observed a modulatory effect of LINC00869 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 LINC00869in vivo, using the tumor xenograft mouse model; and identified a positive correlation between LINC00869 expression levels and the phosphorylation levels of WASP in HCC samples. Overall, our findings suggest a unique mechanism by which LINC00869 orchestrates membrane protrusion during migration and invasion of HCC cells.
LncRNA LINC00869 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.