Long non-coding RNA CCAT2 drives the growth of laryngeal squamous cell carcinoma via regulating YAP activity.

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.

• Authors: Yanzi Zang, Jing Li, Baoluo Wan, Yong Tai, Hongjian Liu, Qian Li, Yuzi Ji
• Journal: Human cell (Hum Cell) Vol. 34 Issue 6 Pg. 1878-1887 (Nov 2021) ISSN: 1749-0774 [Electronic] Japan
• PMID: 34515990 (Publication Type: Journal Article)
• Copyright: © 2021. Japan Human Cell Society.

Chemical References

• Cell Cycle Proteins
• DNA, Neoplasm
• RNA, Long Noncoding
• Transcription Factors
• YY1AP1 protein, human
• long non-coding RNA CCAT2, human
• LATS1 protein, human
• Protein Serine-Threonine Kinases

Topics

• Animals
• Carcinoma, Squamous Cell (genetics, pathology, therapy)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Proliferation (genetics)
• Cell Survival (genetics)
• DNA, Neoplasm (metabolism)
• Disease Models, Animal
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Laryngeal Neoplasms (genetics, pathology, therapy)
• Mice, Nude
• Molecular Targeted Therapy
• Phosphorylation (genetics)
• Protein Binding (genetics)
• Protein Serine-Threonine Kinases (physiology)
• RNA, Long Noncoding (genetics, metabolism, physiology)
• Transcription Factors (genetics, metabolism)
• Tumor Cells, Cultured
• Up-Regulation (genetics)
• Mice