PTBP3 Regulates Proliferation of Lung Squamous Cell Carcinoma Cells Via CDC25A-mediated Cell Cycle Progression

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2022 Jan 12

PMID 35016691

Authors

Yingji Chen

Ying Ji

Suo Liu

Yicai Liu

Wei Feng

Longyu Jin

Affiliations

Soon will be listed here.

Abstract

Background: The roles of Polypyrimidine tract-binding protein 3 (PTBP3) in regulating lung squamous cell carcinoma (LUSC) cells progression is unclear. The aim of this study was to investigate the role of PTBP3 in LUSC.

Methods: Expression and survival analysis of PTBP3 was firstly investigated using TCGA datasets. Quantitative reverse transcription PCR and Western blot were performed to detect PTBP3 expression in clinical samples. Moreover, cell counting kit 8 (CCK-8) assays, colony formation assays and in vivo tumor formation assays were used to examine the effects of PTBP3 on LUSC cell proliferation. RNA-sequence and analysis explores pathways regulated by PTBP3.Flow cytology was used analyzed cell cycle. Cell cycle-related markers were analyzed by Western blot.

Results: PTBP3 was found to be overexpressed in LUSC tissues compared with normal tissues. High PTBP3 expression was significantly correlated with poor prognosis. In vitro and vivo experiments demonstrated that PTBP3 knockdown caused a significant decrease in the proliferation rate of cells. Bioinformatics analysis showed that PTBP3 involved in cell cycle pathway regulation in LUSC. Furthermore, PTBP3 knockdown arrested cell cycle progression at S phase via decreasing CDK2/Cyclin A2 complex. In addition, downregulation of PTBP3 significantly decreased the expression of CDC25A.

Conclusions: Our results suggest that PTBP3 regulated LUSC cell proliferation via cell cycle and might be a potential target for molecular therapy of LUSC.

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References

Liang X, Shi H, Yang L, Qiu C, Lin S, Qi Y . Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells. Br J Cancer. 2017; 116(7):903-911. PMC: 5379144. DOI: 10.1038/bjc.2017.32. View

Hou P, Chen F, Yong H, Lin T, Li J, Pan Y . PTBP3 contributes to colorectal cancer growth and metastasis via translational activation of HIF-1α. J Exp Clin Cancer Res. 2019; 38(1):301. PMC: 6622005. DOI: 10.1186/s13046-019-1312-y. View

Zhang H, Gavin M, Dahiya A, Postigo A, Ma D, Luo R . Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF. Cell. 2000; 101(1):79-89. DOI: 10.1016/S0092-8674(00)80625-X. View

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

Fernandez-Vidal A, Mazars A, Manenti S . CDC25A: a rebel within the CDC25 phosphatases family?. Anticancer Agents Med Chem. 2008; 8(8):825-31. DOI: 10.2174/187152008786847684. View

Al-Matouq J, Holmes T, Hammiller B, Tran N, Holmes M, Freeman S . Accumulation of cytoplasmic CDC25A in cutaneous squamous cell carcinoma leads to a dependency on CDC25A for cancer cell survival and tumor growth. Cancer Lett. 2017; 410:41-49. DOI: 10.1016/j.canlet.2017.09.023. View

Herbst R, Morgensztern D, Boshoff C . The biology and management of non-small cell lung cancer. Nature. 2018; 553(7689):446-454. DOI: 10.1038/nature25183. View

Hou P, Li L, Chen F, Chen Y, Liu H, Li J . PTBP3-Mediated Regulation of ZEB1 mRNA Stability Promotes Epithelial-Mesenchymal Transition in Breast Cancer. Cancer Res. 2017; 78(2):387-398. DOI: 10.1158/0008-5472.CAN-17-0883. View

Liang X, Chen W, Shi H, Gu X, Li Y, Qi Y . PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing. Cell Death Dis. 2018; 9(5):569. PMC: 5948206. DOI: 10.1038/s41419-018-0608-8. View

10.

Shihabudeen Haider Ali M, Cheng X, Moran M, Haemmig S, Naldrett M, Alvarez S . LncRNA Meg3 protects endothelial function by regulating the DNA damage response. Nucleic Acids Res. 2018; 47(3):1505-1522. PMC: 6379667. DOI: 10.1093/nar/gky1190. View

11.

Yam C, Fung T, Poon R . Cyclin A in cell cycle control and cancer. Cell Mol Life Sci. 2002; 59(8):1317-26. PMC: 11337442. DOI: 10.1007/s00018-002-8510-y. View

12.

Raponi M, Zhang Y, Yu J, Chen G, Lee G, Taylor J . Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. Cancer Res. 2006; 66(15):7466-72. DOI: 10.1158/0008-5472.CAN-06-1191. View

13.

Biswas S, Sanphui P, Chatterjee N, Kemeny S, Greene L . Cdc25A phosphatase: a key cell cycle protein that regulates neuron death in disease and development. Cell Death Dis. 2017; 8(3):e2692. PMC: 5386521. DOI: 10.1038/cddis.2017.115. View

14.

Brazao T, Demmers J, van Ijcken W, Strouboulis J, Fornerod M, Romao L . A new function of ROD1 in nonsense-mediated mRNA decay. FEBS Lett. 2012; 586(8):1101-10. DOI: 10.1016/j.febslet.2012.03.015. View

15.

Yamamoto H, Tsukahara K, Kanaoka Y, Jinno S, Okayama H . Isolation of a mammalian homologue of a fission yeast differentiation regulator. Mol Cell Biol. 1999; 19(5):3829-41. PMC: 84229. DOI: 10.1128/MCB.19.5.3829. View

16.

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

17.

Yang X, Qu S, Wang L, Zhang H, Yang Z, Wang J . PTBP3 splicing factor promotes hepatocellular carcinoma by destroying the splicing balance of NEAT1 and pre-miR-612. Oncogene. 2018; 37(50):6399-6413. DOI: 10.1038/s41388-018-0416-8. View

18.

Zappa C, Mousa S . Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016; 5(3):288-300. PMC: 4931124. DOI: 10.21037/tlcr.2016.06.07. View

19.

Sampath D, Shi Z, Plunkett W . Inhibition of cyclin-dependent kinase 2 by the Chk1-Cdc25A pathway during the S-phase checkpoint activated by fludarabine: dysregulation by 7-hydroxystaurosporine. Mol Pharmacol. 2002; 62(3):680-8. DOI: 10.1124/mol.62.3.680. View

20.

Martinez-Alonso D, Malumbres M . Mammalian cell cycle cyclins. Semin Cell Dev Biol. 2020; 107:28-35. DOI: 10.1016/j.semcdb.2020.03.009. View