Human Antigen D (HuD) Promotes Tumorigenesis And Invasion of Small Cell Lung Cancer Via Targeting lncRNA LYPLAL1-DT /miR-204-5P/Profilin 2 Axis

Abstract Background: Small cell lung cancer (SCLC) is one of the most malignant tumors with poor prognosis. RNA-binding protein (RBP) human antigen D (HuD) has been indicated in the process of tumorigenesis and progression of lung tumors, as well as long noncoding RNAs (lncRNA). However, the role of HuD and lncRNA in SCLC remains unknown. Methods: Realtime PCR were used to examine the circulating levels of LYPLAL1-DT in the 46 SCLC patients and 18 normal controls. Assays of dual- luciferase reporter system, RNA pull-down were performed to determine that LYPLAL1-DT could sponge miR-204-5p to upregulate the expression of PFN2. Migration and invasion assay, CCK8 and colony formation assay were used to detect the malignant effect of HuD and LYPLAL1-DT. Tumor xenograft model was established and IHC assay was performed to determine how HuD and LAPLAL1-DT impact in vivo. Results: We revealed that HuD was highly expressed in SCLC tissues and cell lines. HuD boosts the proliferation, migration, invasion of SCLC cells by increasing the PFN2 mRNA stability, which promotes cytoskeleton formation. HuD also enhanced the stability of lncRNA LYPLAL1-DT, which expressed highly in the serum of patients with SCLC and acted as an oncogenic lncRNA in SCLC cells as confirmed in vitro and in vivo. Mechanistically, LYPLAL1-DT functioned as a competing endogenous RNA (ceRNA) for sponging miR-204-5p, leading to the upregulation of its target PFN2 to promote SCLC cell proliferation and invasion. In summary, our data reveal a regulatory pathway in which HuD stabilizes PFN2 mRNA and LYPLAL1-DT, which in turn increases PFN2 expression by binding to miR-204-5p, and ultimately promotes tumorigenesis and invasion in SCLC.Conclusions: Our findings reveal novel regulatory axes involving HuD/PFN2 and lncRNA LYPLAL1-DT/miR-204-5p/PFN2 in the development and progression of small cell lung cancer (SCLC), providing novel prognostic indicators and promising therapeutic targets.