FUBP1 promotes the proliferation of lung squamous carcinoma cells and regulates tumor immunity through PD-L1

Abstract

Background and aim: Lung cancer is a common malignancy. Non-small cell lung cancer (NSCLC) is divided into lung squamous cancer (LUSC), large cell carcinoma, and adenocarcinoma. More than 85% of lung cancer cases are NSCLC patients. Further exploration of the pathogenesis of lung cancer is of great significance. In this study, functions of far upstream element-binding protein 1 (FUBP1) on the proliferation and tumor immunity of LUSC cells were evaluated. Materials and methods: The Cancer Genome Atlas (TCGA) database, Western blot analysis, and immunohistochemistry (IHC) analysis were used to examine the overexpression levels of FUBP1 in LUSC and paracancerous tissues, LUSC cell line, and human normal lung cell line. Then, Western blot assay was employed to validate the transfection efficiency of FUBP1 knockdown in SK-MES-1 cells. Cell counting kit-8 and colony formation assays were used to detect the viability and proliferation of SK-MES-1 cells. Transwell assay was used to examine the migrative and inva-sive abilities of SK-MES-1 cells. Finally, the xenograft tumor mice model was applied to explore the role of FUBP1 in vivo. IHC assay was used to determine the expression levels FUBP1, PD-L1, and Ki-67. Flow cytometry technology was employed to detect the proportion of CD4+ and CD8+ cells in short sequence negative control (sh-NC) and sh-FUBP1 groups. Results: Collectively, the results first indicated that FUBP1 was up-regulated in LUSC tissues and cells. It was also demonstrated that knockdown of FUBP1 suppressed cell migration, invasion, and proliferation in lung squamous carcinoma cells. Finally, knockdown of FUBP1 regulated tumor immunity in vivo. Conclusion: This research suggested that FUBP1 promotes the proliferation of LUSC cells and regulates tumor immunity through programmed death-ligand 1 (PD-L1).

RNA splicing alterations in lung cancer pathogenesis and therapy

“… 72 Compared with the canonical isoform expressed on the surfaces of cancer cells, this PD-L1 isoform appears to be secreted into the tumor immune microenvironment, conferring resistance to anti-PD-L1 immunotherapy in NSCLC. 72 , 73 …”

“… 120 Another recent study indicated that FUBP1 knockdown decreases the expression of PD-L1 and inhibits LUSC tumor growth in vivo. 73 Further investigations are required to reconcile the complex functions and underlying mechanisms of FUBP1 in lung cancer and other cancers.…”

Icariin activates far upstream element binding protein 1 to regulate hypoxia-inducible factor-1α and hypoxia-inducible factor-2α signaling and benefits chondrocytes

“…FUBP1 is known to participate in the malignant process and glycolysis of colon cancer cells by combining with c-Myc ( Wang et al, 2022 ). It promotes the proliferation of lung squamous cell carcinoma cells and regulates tumor immunity through programmed death-ligand 1 (PD-L1) ( Yu et al, 2022 ). Previously, we confirmed ICA-mediated inhibition of FUBP1 expression in SKOV3, a human ovarian cancer cell line ( Wang et al, 2019 ) Thus far, FUBP1 expression and function in chondrocytes have not been fully studied, and the relationship between FUBP1 and HIF-1α/2α in chondrocytes is unclear.…”