Overexpression of CIP2A is an independent prognostic indicator in nasopharyngeal carcinoma and its depletion suppresses cell proliferation and tumor growth
Open accessAbstract
BACKGROUND: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a prognostic marker for several human malignancies. In this study, we investigated the clinical significance of CIP2A and its function in nasopharyngeal carcinoma (NPC). METHODS: Quantitative RT-PCR, western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in NPC cell lines and clinical samples. Kaplan-Meier curves were used to estimate the association between CIP2A expression and patient survival. The functional role of CIP2A in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and xenograft growth. RESULTS: CIP2A levels were upregulated in NPC cell lines and clinical samples at both the mRNA and protein levels (P < 0.01). Patients with high CIP2A expression had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and poorer disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) rates than patients with low CIP2A expression. In addition, CIP2A expression status was an independent prognostic indicator for NPC patients. The depletion of CIP2A expression inhibited c-Myc protein expression in NPC cell lines, suppressed cell viability, colony formation, and anchorage-independent growth in vitro, and inhibited xenograft tumor growth in vivo. CONCLUSIONS: Our data demonstrate that high CIP2A expression in patients was associated with poor survival in NPC, and depletion of CIP2A expression inhibited NPC cell proliferation and tumor growth. Thus, these results warrant further investigation of CIP2A as a novel therapeutic target for the treatment of NPC.
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Targeting CIP2A binding to B56 could constitute a first structure-based strategy for therapeutic inhibition of CIP2A protein stability and activity.
“As functional consequences of high CIP2A protein expression on tumorigenesis are very well established in numerous recent studies [10,14 -18], it is conceivable that targeting of CIP2A binding to B56 could constitute a first structure-based strategy for therapeutic inhibition of CIP2A protein stability and activity.”
From Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56 (2017) · cites this paper as [14]
The therapeutic effect of inhibition of CIP2A protein expression in tumor growth has been validated by numerous studies.
“The therapeutic effect of inhibition of CIP2A protein expression in tumor growth has been recently validated by numerous studies [10,14 -18].”
From Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56 (2017) · cites this paper as [14]
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- Authors
- Liu, N., He, Q.-M., Chen, J.-W., Li, Y.-Q., Xu, Y.-F., Ren, X.-Y., Sun, Y., Mai, H.-Q., Shao, J.-Y., Jia, W.-H., Kang, T.-B., Zeng, M.-S., & Ma, J.
- Affiliations
- Sun Yat-sen University (CN)
- Corresponding author
- Ma, Jun
- Venue
- Molecular Cancer
- Published
- 2014-05-19
- Volume
- 13
- Issue
- 1
- Pages
- 111-111
- ISSN
- 1476-4598 (ISSN-L)
- PMC
- PMC4046003
- OpenAlex
- W2107929060
- Cited by
- 26
- References
- 37
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 3
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Cancer (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81230056)
- Sun Yat-sen University
- Topics
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- CIP2A, nasopharyngeal carcinoma, prognostic factors, oncoprotein, c-Myc, cell proliferation, tumor growth, patient survival, therapeutic target, protein phosphatase 2A inhibitor
- MeSH terms
- Nasopharyngeal Carcinoma, Adult, Aged, Animals, Autoantigens, Carcinoma, Female, Humans, Male, Membrane Proteins, Mice, Nude, Middle Aged, Nasopharyngeal Neoplasms, Neoplasm Staging, Neoplasm Transplantation, Prognosis, Biomarkers, Tumor, Signal Transduction, Gene Expression Regulation, Neoplastic, Survival Analysis, Proto-Oncogene Proteins c-myc, RNA, Small Interfering, Cell Line, Tumor, Tumor Burden, Intracellular Signaling Peptides and Proteins, Cell Proliferation, Mice, Tumor Microenvironment, Neoplasm Grading
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