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Overexpression of splicing factor poly(rC)-binding protein 1 elicits cycle arrest, apoptosis induction, and p73 splicing in human cervical carcinoma cells

  • Original Article – Cancer Research
  • Published:
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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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Data availability

The data presented in this study are available in the article.

Abbreviations

PCBP1:

Poly(rC)-binding protein 1

DNp73:

N-terminally truncated p73

TAp73:

Transactivating p73

EMT:

Epithelial-mesenchymal transition

CD44:

Cluster differentiation-44

Bax:

Bcl-2-Associated X

Bcl-2:

B-cell CLL/lymphoma 2

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Funding

This work was supported by grants of the national Key R&D project of the Chinese Ministry of Science and Technology (2018YFE0205100), the Key Program of the National Natural Science Foundation of China (U1632270), the National Natural Science Foundation of China (11675234, 11875061), and the Natural Science Foundation of Gansu (17JR5RA310).

Author information

Author notes

  1. Yuhong Chen and Zhihui Dou have contributed equally to this work.

Authors and Affiliations

  1. Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China

    Yuhong Chen, Zhihui Dou, Xiaohua Chen, Dapeng Zhao, Wei Su, Taotao Zhang, Caipeng Xu, Huiweng Lei, Qiang Li, Hong Zhang & Cuixia Di

  2. Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China

    Yuhong Chen, Zhihui Dou, Xiaohua Chen, Dapeng Zhao, Wei Su, Taotao Zhang, Caipeng Xu, Huiweng Lei, Qiang Li, Hong Zhang & Cuixia Di

  3. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100039, China

    Yuhong Chen, Zhihui Dou, Xiaohua Chen, Dapeng Zhao, Wei Su, Taotao Zhang, Caipeng Xu, Huiweng Lei, Qiang Li, Hong Zhang & Cuixia Di

  4. School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, 100039, China

    Yuhong Chen, Zhihui Dou, Xiaohua Chen, Dapeng Zhao, Wei Su, Taotao Zhang, Caipeng Xu, Huiweng Lei, Qiang Li, Hong Zhang & Cuixia Di

  5. Laboratory of Precision Medicine and Translational Medicine, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou Science and Technology Town Hospital, Suzhou, 215153, China

    Tuanjie Che

  6. Key Laboratory of Functional Genomic and Molecular Diagnosis of Gansu Province, Lanzhou, 730030, China

    Tuanjie Che

  7. Department of Biotherapy Center, Gansu Provincial Hospital, Lanzhou, Gansu, China

    Tao Qu

  8. Department of Heavy Ion Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China

    Qiang Li, Hong Zhang & Cuixia Di

Authors
  1. Yuhong Chen
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  2. Zhihui Dou
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  3. Xiaohua Chen
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  4. Dapeng Zhao
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  5. Tuanjie Che
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  6. Wei Su
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  8. Taotao Zhang
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  9. Caipeng Xu
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  10. Huiweng Lei
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  11. Qiang Li
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  12. Hong Zhang
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  13. Cuixia Di
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Contributions

YH Chen, ZH Dou, CX Di and HZ Hong and Q Li conceived the manuscript. YH Chen, CX Di, ZH Dou and XH Chen consulted the literature and wrote the initial draft of the manuscript. DP Zhao, TJ Che, W Su, T Qu, TT Zhang, CP Xu and HW Lei participated in writing the manuscript. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Qiang Li, Hong Zhang or Cuixia Di.

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Chen, Y., Dou, Z., Chen, X. et al. Overexpression of splicing factor poly(rC)-binding protein 1 elicits cycle arrest, apoptosis induction, and p73 splicing in human cervical carcinoma cells. J Cancer Res Clin Oncol 148, 3475–3484 (2022). https://doi.org/10.1007/s00432-022-04170-3

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