Heliyon (Nov 2024)
LINC01857 promotes cell proliferation and migration while dampening cell apoptosis in pancreatic cancer by upregulating CDC42EP3 via miR-450b-5p
Abstract
Background: Pancreatic cancer (PC) is a devastating human malignancy with a poor survival outcome (5-year survival less than 10 %). In recent years, the regulatory roles of long non-coding RNAs (lncRNAs) in various types of cancers have been widely reported. Based on bioinformatics analysis, LINC01857 is shown to be highly expressed in PC tissue. Nevertheless, the role of LINC01857 in PC is limitedly reported. Hence, this study aimed to explore the effects of lncRNA LINC01857 on PC cell process and the related mechanism. Methods: RT-qPCR and fluorescence in situ hybridization (FISH) assay were conducted to measure LINC01857 expression and distribution in PANC-1 and MIA PaCa-2 cells. Colony formation and wound healing assays as well as flow cytometry analyses were employed to estimate the proliferation, migration, and apoptosis of PC cells transfected with pcDNA3.1-LINC01857 or si-LINC01857 compared with the behavior of PC cells transfected with empty pcDNA3.1 vector (control) or si-negative control (NC). Furthermore, RNA pulldown and luciferase reporter assays were utilized to demonstrate the interaction of LINC01857 and miR-450b-5p or to validate the binding of miR-450b-5p and cell division cycle 42 effector protein 3 (CDC42EP3). Results: LINC01857 was highly expressed in PANC-1 and MIA PaCa-2 cells in contrast to its expression in pancreatic ductal epithelial cells (8.9 folds and 7.1 folds, p < 0.001). Silencing LINC01857 significantly reduced cell proliferation and migration while enhancing apoptosis (p < 0.0005). In contrast, overexpression of LINC01857 markedly (p < 0.05) accelerated these malignant behavior of PC cells. MiR-450b-5p was targeted and inversely regulated by LINC01857. Moreover, CDC42EP3 was verified to be targeted by miR-450b-5p, and CDC42EP3 was correlated to LINC01857 in a positive manner (p < 0.001). Rescue experiments manifested that silencing CDC42EP3 effectively (p < 0.05) reversed the promoting effect of LINC01857 on malignant behavior of PC cells. Conclusion: LINC01857 promotes PC cell proliferation and migration while obstructing cell apoptosis by binding to miR-450b-5p and thus regulating CDC42EP3 expression. The study presents a novel and promising regulatory axis, which holds potential for the identification of biomarkers and development of therapeutic strategies for PC treatment.
