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Molecular Cancer Research
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Cancer Genes and Networks

PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E

Xiaonan Wang, Qianying Guo, Hao Wang, Xiaodong Yuan, Bijun Wang, Peter E. Lobie, Tao Zhu, Sheng Tan and Zhengsheng Wu
Xiaonan Wang
1Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
2Laboratory of Pathogenic Microbiology and Immunology, Anhui Medical University, Hefei, Anhui, China.
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Qianying Guo
1Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
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Hao Wang
1Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
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Xiaodong Yuan
1Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
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Bijun Wang
1Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
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Peter E. Lobie
3Tsinghua-Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School and Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
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Tao Zhu
4Laboratory of Molecular Tumor Pathology, School of Life Science, University of Science and Technology of China, Hefei, Anhui, China.
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  • For correspondence: woozson@yahoo.com tansheng@mail.ustc.edu.cn zhut@ustc.edu.cn
Sheng Tan
4Laboratory of Molecular Tumor Pathology, School of Life Science, University of Science and Technology of China, Hefei, Anhui, China.
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  • For correspondence: woozson@yahoo.com tansheng@mail.ustc.edu.cn zhut@ustc.edu.cn
Zhengsheng Wu
1Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
5Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
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  • For correspondence: woozson@yahoo.com tansheng@mail.ustc.edu.cn zhut@ustc.edu.cn
DOI: 10.1158/1541-7786.MCR-20-0390 Published January 2021
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Abstract

It is commonly accepted that cellular protein levels are primarily determined by mRNA levels. However, discordance between protein and mRNA expression has been implicated in many pathologic conditions including oncogenesis. The mechanisms involved in this discordance are complicated and far from understood. In this study, it was observed that the expression levels of poly(C) binding protein 2 (PCBP2) mRNA and protein were diametric in breast normal and cancer cell lines, paraffin-embedded and fresh tissue specimens, consistent with data from The Cancer Genome Atlas and the Clinical Proteomic Tumor Analysis Consortium. Moreover, PCBP2 protein expression was significantly associated with disease progression and poor outcome in patients with breast cancer. Depletion of PCBP2 protein inhibited cell proliferation, colony formation, migration, invasion, and in vivo tumor growth and metastasis. Forced expression of PCBP2 exhibited the opposite effect. Mechanistically, it was demonstrated that PCBP2 3′ untranslated region (3′UTR) was subject to alternative splicing and polyadenylation (APA) in breast cancer tissues and cell lines. Non-full-length 3′UTR PCBP2 transcripts yielded more protein than the full-length 3′UTR transcripts and enhanced the oncogenic and metastatic capacities of human breast cancer cells. Furthermore, UFD1 and NT5E were identified as genes downstream of PCBP2. PCBP2 promoted oncogenicity of breast cancer cells via upregulation of the expression of UFD1 and NT5E by direct binding to their 3′UTR-B portions.

Implications: Findings demonstrate that APA of PCBP2 3′UTR contributes to its increased expression with subsequent promotion of breast cancer progression by regulating UFD1 and NT5E.

Visual Overview: http://mcr.aacrjournals.org/content/molcanres/19/1/86/F1.large.jpg.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/).

  • Mol Cancer Res 2021;19:86–98

  • Received April 29, 2020.
  • Revision received August 27, 2020.
  • Accepted October 6, 2020.
  • Published first October 9, 2020.
  • ©2020 American Association for Cancer Research.
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Molecular Cancer Research: 19 (1)
January 2021
Volume 19, Issue 1
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PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E
Xiaonan Wang, Qianying Guo, Hao Wang, Xiaodong Yuan, Bijun Wang, Peter E. Lobie, Tao Zhu, Sheng Tan and Zhengsheng Wu
Mol Cancer Res January 1 2021 (19) (1) 86-98; DOI: 10.1158/1541-7786.MCR-20-0390

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PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E
Xiaonan Wang, Qianying Guo, Hao Wang, Xiaodong Yuan, Bijun Wang, Peter E. Lobie, Tao Zhu, Sheng Tan and Zhengsheng Wu
Mol Cancer Res January 1 2021 (19) (1) 86-98; DOI: 10.1158/1541-7786.MCR-20-0390
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Molecular Cancer Research
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