Abstract
Emerging evidence suggests that long non-coding RNA (lncRNA) is closely associated with numerous human diseases, including cancer. However, the functional relevance of lncRNA in human laryngeal squamous cell carcinoma (LSCC) is largely unknown. In the current study, we described CCAT2, a previously unappreciated oncogenic lncRNA in LSCC. CCAT2 was significantly upregulated in human LSCC tissue and serum samples, associated with larger tumor volume, higher clinical stage, and poorer differentiation status. Lentivirus-mediated CCAT2 knockdown notably repressed the cell viability, colony formation, and DNA synthesis rate of LSCC. Screening of transcription factors revealed that YAP/TEAD activity was affected by CCAT2 in LSCC cells. Further, CCAT2 directly binds to YAP protein and blocks the phosphorylation of YAP induced by LATS1, resulting in the nuclear translocation of YAP and the activation of YAP oncogenic targets, such as CTGF, CYR61 and AMOTL2. Importantly, we also confirmed the regulation of CCAT2 on YAP activity in vivo based on nude mice model. Altogether, we identified a novel lncRNA that controls YAP nucleocytoplasmic shuttling and promotes LSCC cell proliferation. Given the importance of YAP in tumorigenesis and progression, our results provide insights to intervene LSCC by targeting the CCAT2/YAP axis.
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The work is funded by Henan Province Science and Technology Tackling Project (201201702196702196).
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Contributions: (I) Conception and design: HJ Liu; (II) Administrative support: HJ Liu; (III) Provision of study materials or patients: YZ Zang; (IV) Collection and assembly of data: J Li, BL Wan, Y Tai, Q Li, YZ Ji; (V) Data analysis and interpretation: YZ Zang; (VI) Manuscript writing: YZ Zang; (VII) Final approval of manuscript: all authors.
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The Ethics Committee of the People's Hospital of Henan Province approved the use of human tissue samples (No.YYNH-00368X), and the experimental steps were conducted in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Institutional Animal Care and Use Committee of People's Hospital of Henan Province approved all animal care, use, and euthanasia (No.YYNH-00368X), which were handled in strict accordance with the “Guide for the Care and Use of Laboratory Animals” and the “Principles for the Utilization and Care of Vertebrate Animals”.
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Zang, Y., Li, J., Wan, B. et al. Long non-coding RNA CCAT2 drives the growth of laryngeal squamous cell carcinoma via regulating YAP activity. Human Cell 34, 1878–1887 (2021). https://doi.org/10.1007/s13577-021-00606-z
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DOI: https://doi.org/10.1007/s13577-021-00606-z