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Cancer Sci. 2018 Sep;109(9):2717-2733. doi: 10.1111/cas.13745.

HOTAIR, a long noncoding RNA, is a marker of abnormal cell cycle regulation in lung cancer.

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Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
Emergency Department, Tianjin Medical University General Hospital, Tianjin, China.
Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Tianjin Neurological Institute, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin, China.


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.


EMT; HOTAIR; cell cycle; lung cancer; β-catenin

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