Pumilio RNA Binding Family Member 2 Promotes the Proliferation and Metastasis of Lung Cancer Cells by Regulating Ca2+ Signaling Pathway via Targeting C-X-C Chemokine Receptor Type 4

Abstract

The aim of the present study was to investigate the mechanism by which pumilio RNA binding family member 2 (PUM2), an RNA-binding protein (RBP) of C-X-C chemokine receptor type 4 (CXCR4), exerts its effects on the development of lung cancer. RT-qPCR and western blot analysis were utilized to measure the expression of PUM2 in several lung cancer cell lines. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell- and wound healing assays were employed to determine the proliferation, invasion and migration of NCI-H520 cells, respectively. Next, the expression of CXCR4 was measured using western blot analysis, and the combination between PUM2 and CXCR4 was verified by RNA immunoprecipitation (RIP) assay and RNA pull down assay. Finally, whether the expression of PUM2 can affect the Ca2+ signaling pathway was confirmed by western blot assay. Results revealed that the expression level of PUM2 was notably upregulated in lung cancer cells, and knockdown of PUM2 significantly inhibited the proliferation, invasion and migration of NCI-H520 cells. PUM2 was confirmed to be the RBP of CXCR4, and PUM2 knockdown decreased the expression of CXCR4. In addition, PUM2 silencing inhibited the phosphorylation of CaMKII, ERK, and MEK. Taken together, these findings demonstrated that PUM2 could promote the proliferation and metastasis of lung cancer cells by regulating Ca2+ signaling pathway via targeting CXCR4, which may provide a novel insight for the future treatment of lung cancer.