Overexpression of Splicing Factor Poly(rC)-binding Protein 1 Elicits Cycle Arrest, Apoptosis Induction, and P73 Splicing in Human Cervical Carcinoma Cells

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2022 Jul 27

PMID 35896897

Authors

Yuhong Chen

Zhihui Dou

Xiaohua Chen

Dapeng Zhao

Tuanjie Che

Wei Su

Tao Qu

Taotao Zhang

Caipeng Xu

Huiweng Lei

Qiang Li

Hong Zhang

Cuixia Di

Affiliations

Soon will be listed here.

Abstract

Purpose: Splicing factor poly(rC)-binding protein 1 (PCBP1) is a novel tumor suppressor that is downregulated in several cancers thereby regulating tumor formation and metastasis. However, the involvement of PCBP1 in apoptosis of cancer cells and the molecular mechanism remains elusive. On this basis, we sought to investigate the role of splicing factor PCBP1 in the apoptosis in human cervical cancer cells.

Methods: To investigate PCBP1 functions in vitro, we overexpressed PCBP1 in human cervical cancer cells. A series of cytological function assays were employed to study to the role of PCBP1 in cell proliferation, cell cycle arrest and apoptosis.

Results: Overexpression of PCBP1 was found to greatly repress proliferation of HeLa cells in a time-dependent manner. It also induced a significant increase in G2/M phase arrest and apoptosis. Furthermore, overexpressed PCBP1 favored the production of long isoforms of p73, thereby inducing upregulated ratio of Bax/Bcl-2, the release of cytochrome c and the expression of caspase-3.

Conclusion: Our results revealed that PCBP1 played a vital role in p73 splicing, cycle arrest and apoptosis induction in human cervical carcinoma cells. Targeting PCBP1 may be a potential therapeutic strategy for cervical cancer therapy.

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References

Aasheim H, Loukianova T, Deggerdal A, Smeland E . Tissue specific expression and cDNA structure of a human transcript encoding a nucleic acid binding [oligo(dC)] protein related to the pre-mRNA binding protein K. Nucleic Acids Res. 1994; 22(6):959-64. PMC: 307915. DOI: 10.1093/nar/22.6.959. View

Barboro P, Ferrari N, Balbi C . Emerging roles of heterogeneous nuclear ribonucleoprotein K (hnRNP K) in cancer progression. Cancer Lett. 2014; 352(2):152-9. DOI: 10.1016/j.canlet.2014.06.019. View

Chaudhury A, Chander P, Howe P . Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: Focus on hnRNP E1's multifunctional regulatory roles. RNA. 2010; 16(8):1449-62. PMC: 2905745. DOI: 10.1261/rna.2254110. View

Chkheidze A, Liebhaber S . A novel set of nuclear localization signals determine distributions of the alphaCP RNA-binding proteins. Mol Cell Biol. 2003; 23(23):8405-15. PMC: 262676. DOI: 10.1128/MCB.23.23.8405-8415.2003. View

Choi H, Kim C, Hwang C, Song K, Law P, Wei L . Novel function of the poly(C)-binding protein alpha CP3 as a transcriptional repressor of the mu opioid receptor gene. FASEB J. 2007; 21(14):3963-73. DOI: 10.1096/fj.07-8561com. View

Dejgaard K, Leffers H . Characterisation of the nucleic-acid-binding activity of KH domains. Different properties of different domains. Eur J Biochem. 1996; 241(2):425-31. DOI: 10.1111/j.1432-1033.1996.00425.x. View

Di C, Han L, Zhang H, Xu S, Mao A, Sun C . Diallyl disulfide attenuated carbon ion irradiation-induced apoptosis in mouse testis through changing the ratio of Tap73/ΔNp73 via mitochondrial pathway. Sci Rep. 2015; 5:16020. PMC: 4630619. DOI: 10.1038/srep16020. View

Di C, Syafrizayanti , Zhang Q, Chen Y, Wang Y, Zhang X . Function, clinical application, and strategies of Pre-mRNA splicing in cancer. Cell Death Differ. 2018; 26(7):1181-1194. PMC: 6748147. DOI: 10.1038/s41418-018-0231-3. View

Gomez L, Sottile M, Guerrero-Gimenez M, Zoppino F, Redondo A, Gago F . DNA methylation and upregulation of ΔNp73 are associated with an adverse prognosis in breast cancer. J Clin Pathol. 2017; 71(1):52-58. DOI: 10.1136/jclinpath-2017-204499. View

10.

Holtkamp N, Atallah I, Okuducu A, Mucha J, Hartmann C, Mautner V . MMP-13 and p53 in the progression of malignant peripheral nerve sheath tumors. Neoplasia. 2007; 9(8):671-7. PMC: 1950437. DOI: 10.1593/neo.07304. View

12.

Ishii T, Hayakawa H, Igawa T, Sekiguchi T, Sekiguchi M . Specific binding of PCBP1 to heavily oxidized RNA to induce cell death. Proc Natl Acad Sci U S A. 2018; 115(26):6715-6720. PMC: 6042155. DOI: 10.1073/pnas.1806912115. View

13.

Ji F, Wu Y, An Z, Liu X, Jiang J, Chen F . Expression of both poly r(C) binding protein 1 (PCBP1) and miRNA-3978 is suppressed in peritoneal gastric cancer metastasis. Sci Rep. 2017; 7(1):15488. PMC: 5686074. DOI: 10.1038/s41598-017-15448-9. View

14.

Jiang P, Li Z, Tian F, Li X, Yang J . Fyn/heterogeneous nuclear ribonucleoprotein E1 signaling regulates pancreatic cancer metastasis by affecting the alternative splicing of integrin β1. Int J Oncol. 2017; 51(1):169-183. PMC: 5467783. DOI: 10.3892/ijo.2017.4018. View

15.

Jin P, Tan Y, Zhang W, Li J, Wang K . Prognostic alternative mRNA splicing signatures and associated splicing factors in acute myeloid leukemia. Neoplasia. 2020; 22(9):447-457. PMC: 7356271. DOI: 10.1016/j.neo.2020.06.004. View

16.

Kwak H, Song W, Lawler J . Exercise training attenuates age-induced elevation in Bax/Bcl-2 ratio, apoptosis, and remodeling in the rat heart. FASEB J. 2006; 20(6):791-3. DOI: 10.1096/fj.05-5116fje. View

17.

Liu S, Chan K, Leung R, Law H, Leung T, Ngan H . Enhancement of the radiosensitivity of cervical cancer cells by overexpressing p73alpha. Mol Cancer Ther. 2006; 5(5):1209-15. DOI: 10.1158/1535-7163.MCT-05-0451. View

18.

Liu Y, Gai L, Liu J, Cui Y, Zhang Y, Feng J . Expression of poly(C)-binding protein 1 (PCBP1) in NSCLC as a negative regulator of EMT and its clinical value. Int J Clin Exp Pathol. 2015; 8(6):7165-72. PMC: 4525944. View

19.

Lu J, Gao F . Role and molecular mechanism of heterogeneous nuclear ribonucleoprotein K in tumor development and progression. Biomed Rep. 2016; 4(6):657-663. PMC: 4887935. DOI: 10.3892/br.2016.642. View

20.

Lu X, Jiang L, Zhang L, Zhu Y, Hu W, Wang J . Immune Signature-Based Subtypes of Cervical Squamous Cell Carcinoma Tightly Associated with Human Papillomavirus Type 16 Expression, Molecular Features, and Clinical Outcome. Neoplasia. 2019; 21(6):591-601. PMC: 6658934. DOI: 10.1016/j.neo.2019.04.003. View

21.

Lucena-Araujo A, Kim H, Thome C, Jacomo R, Melo R, Bittencourt R . High ΔNp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia. Blood. 2015; 126(20):2302-6. PMC: 4760128. DOI: 10.1182/blood-2015-01-623330. View