HOTAIR, a long noncoding RNA, is a marker of abnormal cell cycle regulation in lung cancer
Minghui Liu1, Hongyi Zhang1, Ying Li2
1Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Abstract:
Dysregulation of the cell cycle is a key indicator of tumors, including lung cancer. Recently, the study of cell cycle inhibitors has made great progress in relation to lung cancer. However, the question of what kinds of patients can use cell cycle inhibitors has plagued us. Therefore, seeking an accurate and convenient marker for the abnormal cell cycle in lung cancer is very important. In the present research, we showed that lncRNA HOTAIR is an optimal indicator of cell cycle dysregulation in lung cancer. In the present study, we investigated HOTAIR-specific expression in lung primary tumor samples by analyzing the TCGA public database and 67 pairs of patients' tissues collected from our department. Through the TCGA public database KEGG analysis, HOTAIR correlates with the cell cycle pathway. We identified that HOTAIR and its 2 segments, HOTAIR3' and HOTAIR5', promote the cell cycle passing through the restriction point during G1-S phase by regulating the Rb-E2F pathway and influence non-small-cell lung cancer cell proliferation, migration and invasion through epithelial-mesenchymal transition (EMT) and the β-catenin pathway in vitro and vivo. Finally, we showed that the high expression of HOTAIR was associated with resistance to gefitinib through the dysregulated cell cycle. In conclusion, HOTAIR could be an ideal indicator of cell cycle dysregulation and guide the use of cell cycle inhibitors.
Insights
Long non-coding RNA HOTAIR indicates abnormal cell cycles in lung cancer. High HOTAIR expression correlates with gefitinib resistance, guiding the use of cell cycle inhibitors for lung cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cell cycle dysregulation is a hallmark of lung cancer.
- Identifying reliable biomarkers for cell cycle abnormalities is crucial for targeted therapies.
- Cell cycle inhibitors show promise but patient selection remains a challenge.
Purpose of the Study:
- To determine if long non-coding RNA HOTAIR can serve as a biomarker for cell cycle dysregulation in lung cancer.
- To investigate the role of HOTAIR in non-small-cell lung cancer progression and treatment resistance.
Main Methods:
- Analysis of HOTAIR expression in The Cancer Genome Atlas (TCGA) database and patient tumor tissues.
- KEGG pathway analysis to identify correlations between HOTAIR and the cell cycle.
- In vitro and in vivo experiments to assess HOTAIR's impact on cell cycle progression, proliferation, migration, invasion, EMT, and the β-catenin pathway.
- Correlation analysis between HOTAIR expression and gefitinib resistance.
Main Results:
- HOTAIR expression is significantly correlated with the cell cycle pathway in lung cancer.
- HOTAIR and its segments (HOTAIR3', HOTAIR5') promote G1-S phase transition via the Rb-E2F pathway.
- HOTAIR influences non-small-cell lung cancer cell proliferation, migration, and invasion through EMT and the β-catenin pathway.
- High HOTAIR expression is associated with gefitinib resistance due to cell cycle dysregulation.
Conclusions:
- Long non-coding RNA HOTAIR is an optimal indicator of cell cycle dysregulation in lung cancer.
- HOTAIR plays a critical role in promoting lung cancer progression and influencing treatment response.
- HOTAIR expression levels can guide the clinical application of cell cycle inhibitors and predict resistance to targeted therapies like gefitinib.
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