2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.03D.02 HNRNPC-Regulated PA2G4 Promotes Proliferation and Metastasis of LUAD Cells

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The study conducted by Jinghua Chen at Guangzhou Twelfth People's Hospital investigates the role of the RNA-binding protein HNRNPC and its regulation of PA2G4 in the context of lung adenocarcinoma (LUAD). HNRNPC is found to be highly expressed in LUAD tissues, particularly associated with poor prognosis, and plays a crucial role in pre-mRNA processing. This research aims to elucidate the mechanism by which HNRNPC and PA2G4 contribute to LUAD cell proliferation and metastasis.<br /><br />The study identifies two different polyadenylate (PolyA) site transcripts of PA2G4 mRNA, termed PA2G4-L and PA2G4-S. HNRNPC overexpression results in an increased level of the shorter PA2G4-S, promoting stability and enhancing LUAD cell proliferation and metastasis. Conversely, inhibition of HNRNPC leads to reduced levels of PA2G4-T, increased PA2G4-L, decreased PA2G4-S, and reduced mRNA stabilization. Techniques such as 3’RACE-electrophoresis, RNA pulldown, RNA binding protein immunoprecipitation (RIP), and luciferase reporter assays confirm the binding interaction between HNRNPC and PA2G4 mRNA. <br /><br />Experimental methods employed include qRT-PCR for gene expression analysis, western blotting for protein level detection, and Actinomycin D treatment for evaluating RNA stabilization. Cell proliferation is analyzed through the CCK8 assay and colony formation assays, while flow cytometry is used to assess the cell cycle, and Transwell assays are performed to examine cell migration and invasion capabilities.<br /><br />The findings present that HNRNPC facilitates the stabilization of PA2G4-S mRNA by inducing an advanced PolyA site, thereby promoting LUAD cell growth and metastatic potential. The overexpression of both PA2G4 variants increases LUAD cell proliferation and metastasis, with PA2G4-S showing a more pronounced effect. These insights contribute to understanding how HNRNPC and PA2G4 play a significant role in LUAD progression.

Asset Subtitle

Jing-Hua Chen

Meta Tag

Speaker Jing-Hua Chen

Topic Tumor Biology – Translational Biology

Keywords

HNRNPC

PA2G4

lung adenocarcinoma

RNA-binding protein

mRNA stabilization

cell proliferation

metastasis

polyadenylate site

gene expression

protein interaction