FUBP1 promotes the proliferation of lung squamous carcinoma cells and regulates tumor immunity through PD-L1
Main Article Content
Keywords
FUBP1, LUSC, PD-L1, proliferation, tumor immunity
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 invasive 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).
References
2. Hsu PC, Jablons DM, Yang CT, You L. Epidermal growth factor receptor (EGFR) pathway, Yes-associated protein (YAP) and the regulation of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). Int J Mol Sci. 2019;20(15):3821. 10.3390/ijms20153821
3. Jiang P, Huang M, Qi W, Wang F, Yang T, Gao T, et al. FUBP1 promotes neuroblastoma proliferation via enhancing glycolysis—A new possible marker of malignancy for neuroblastoma. J Exp Clin Cancer Res. 2019;38(1):400. 10.1186/s13046-019-1414-6
4. Singer S, Malz M, Herpel E, Warth A, Bissinger M, Keith M, et al. Coordinated expression of stathmin family members by far upstream sequence element-binding protein-1 increases motility in non-small cell lung cancer. Cancer Res. 2009;69(6):2234–43. 10.1158/0008-5472.CAN-08-3338
5. Dong Y, Huaying S, Danying W, Chihong Z, Ruibin J, Xiaojiang S, et al. Significance of methylation of FBP1 gene in non-small cell lung cancer. BioMed Res Int. 2018;2018:3726091. 10.1155/2018/3726091
6. World Medical Association. World Medical Association declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4. 10.1001/jama.2013.281053
7. Kang M, Kim HJ, Kim TJ, Byun JS, Lee JH, Lee DH, et al. Multiple functions of Fubp1 in cell cycle progression and cell survival. Cells. 2020;9(6):1347. 10.3390/cells9061347
8. Zhong Q, Liu ZH, Lin ZR, Hu ZD, Yuan L, Liu YM, et al. The RARS-MAD1L1 fusion gene induces cancer stem cell-like properties and therapeutic resistance in nasopharyngeal carcinoma. Clin Cancer Res. 2018;24(3):659–73. 10.1158/1078-0432.CCR-17-0352
9. Elman JS, Ni TK, Mengwasser KE, Jin D, Wronski A, Elledge SJ, et al. Identification of FUBP1 as a long tail cancer driver and widespread regulator of tumor suppressor and oncogene alternative splicing. Cell Rep. 2019;28(13):3435–49.e5. 10.1016/j.celrep.2019.08.060
10. Debaize L, Troadec MB. The master regulator FUBP1: Its emerging role in normal cell function and malignant development. Cell Mol Life Sci (CMLS). 2019;76(2):259–81. 10.1007/s00018-018-2933-6
11. Larsen TV, Hussmann D, Nielsen AL. PD-L1 and PD-L2 expression correlated genes in non-small-cell lung cancer. Cancer Comm. 2019;39(1):30. 10.1186/s40880-019-0376-6
12. Tanegashima T, Togashi Y, Azuma K, Kawahara A, Ideguchi K, Sugiyama D, et al. Immune suppression by PD-L2 against spontaneous and treatment-related antitumor immunity. Clin Cancer Res. 2019;25(15):4808–19. 10.1158/1078-0432.CCR-18-3991
13. Aiba T, Hattori C, Sugisaka J, Shimizu H, Ono H, Domeki Y, et al. Gene expression signatures as candidate biomarkers of response to PD-1 blockade in non-small cell lung cancers. PloS One. 2021;16(11):e0260500. 10.1371/journal.pone.0260500
14. Zhang Z, Li L, Li M, Wang X. The SARS-CoV-2 host cell receptor ACE2 correlates positively with immunotherapy response and is a potential protective factor for cancer progression. Comput Struct Biotechnol J. 2020;18:2438–44. 10.1016/j.csbj.2020.08.024
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.