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A systematic analysis of orphan cyclins reveals CNTD2 as a new oncogenic driver in lung cancer
L Gasa1, A Sanchez-Botet1, E Quandt1
1Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain.
Abstract:
As lung cancer has increased to the most common cause of cancer death worldwide, prognostic biomarkers and effective targeted treatments remain lacking despite advances based on patients' stratification. Multiple core cyclins, best known as drivers of cell proliferation, are commonly deregulated in lung cancer where they may serve as oncogenes. The recent expansion of the cyclin family raises the question whether new members might play oncogenic roles as well. Here, we investigated the protein levels of eight atypical cyclins in lung cancer cell lines and formalin-fixed and paraffin-embedded (FFPE) human tumors, as well as their functional role in lung cancer cells. Of the new cyclins evaluated, CNTD2 was significantly overexpressed in lung cancer compared to adjacent normal tissue, and exhibited a predominant nuclear location. CNTD2 overexpression increased lung cancer cell viability, Ki-67 intensity and clonogenicity and promoted lung cancer cell migration. Accordingly, CNTD2 enhanced tumor growth in vivo on A549 xenograft models. Finally, the analysis of gene expression data revealed a high correlation between elevated levels of CNTD2 and decreased overall survival in lung cancer patients. Our results reveal CNTD2 as a new oncogenic driver in lung cancer, suggesting value as a prognostic biomarker and therapeutic target in this disease.
Insights
New research identifies CNTD2 as a significant oncogenic driver in lung cancer. Overexpression of this cyclin promotes cancer cell growth and migration, suggesting its potential as a prognostic biomarker and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Lung cancer is a leading cause of cancer death globally, with a need for better prognostic biomarkers and targeted treatments.
- Core cyclins are known oncogenes in lung cancer, driving cell proliferation.
- The oncogenic potential of newly identified atypical cyclins in lung cancer requires investigation.
Purpose of the Study:
- To investigate the protein levels and functional roles of eight atypical cyclins in lung cancer.
- To determine if novel cyclins contribute to lung cancer development and progression.
Main Methods:
- Protein levels of eight atypical cyclins were analyzed in lung cancer cell lines and formalin-fixed, paraffin-embedded (FFPE) human tumors.
- Functional roles were assessed in lung cancer cells, including viability, proliferation (Ki-67), clonogenicity, and migration assays.
- In vivo tumor growth was evaluated using A549 xenograft models.
- Gene expression data was analyzed for correlations between CNTD2 levels and patient survival.
Main Results:
- Cyclin-dependent kinase andnotin-like domain containing 2 (CNTD2) was significantly overexpressed in lung cancer compared to normal tissue, with nuclear localization.
- CNTD2 overexpression enhanced lung cancer cell viability, Ki-67 intensity, clonogenicity, and migration.
- CNTD2 promoted tumor growth in vivo in A549 xenograft models.
- Elevated CNTD2 levels correlated with decreased overall survival in lung cancer patients.
Conclusions:
- CNTD2 acts as a novel oncogenic driver in lung cancer.
- CNTD2 demonstrates potential as a prognostic biomarker for lung cancer.
- CNTD2 represents a promising therapeutic target for lung cancer treatment.
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