2. Academic Validation
  3. YTHDC1-Mediated lncRNA MSC-AS1 m6A Modification Potentiates Laryngeal Squamous Cell Carcinoma Development via Repressing ATXN7 Transcription

YTHDC1-Mediated lncRNA MSC-AS1 m6A Modification Potentiates Laryngeal Squamous Cell Carcinoma Development via Repressing ATXN7 Transcription

  • Mol Biotechnol. 2024 Apr 18. doi: 10.1007/s12033-024-01150-5.
Shu Zhang 1 2,  Qun Wu 1,  Wei Cheng 3,  Weijiang Dong 4,  Bo Kou 5
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road, Yanta District, Xi'an, 710061, Shaanxi, People's Republic of China.
  • 2 Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, Inner Mongolia, People's Republic of China.
  • 3 Department of General Surgery, Danfeng County Hospital, Shangluo, 726200, Shaanxi, People's Republic of China.
  • 4 Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, People's Republic of China.
  • 5 Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road, Yanta District, Xi'an, 710061, Shaanxi, People's Republic of China. BoKouxy@163.com.
PMID: 38637450 DOI: 10.1007/s12033-024-01150-5
Abstract

Laryngeal squamous cell carcinoma (LSCC) has the highest mortality rate among head and neck squamous cell carcinoma. This study was designed to investigate the biological effect of long noncoding RNA (lncRNA) MSC antisense RNA 1 (MSC-AS1) on LSCC development and the underlying mechanism. The expression and prognostic value of lncRNAs in head and neck squamous cell carcinoma were predicted in the bioinformatics tools. The overexpression of MSC-AS1 in LSCC patients predicted a poor prognosis. Depletion of MSC-AS1 using shRNA repressed the malignant phenotype of AMC-HN-8 and TU-177 cells. MSC-AS1, mainly localized in the nucleus, interacted closely with the transcription factor CCCTC-binding factor (CTCF). CTCF played anti-tumor effects in vitro and in vivo. Ataxin-7 (ATXN7) was predicted to be a downstream target of CTCF, whose expression was negatively controlled by MSC-AS1. MSC-AS1 was found to block the expression of CTCF, thereby repressing ATXN7. Finally, MSC-AS1 overexpression in LSCC was governed by YTH domain-containing protein 1 (YTHDC1)-mediated m6A modification. In summary, our research identified the YTHDC1/MSC-AS1/CTCF/ATXN7 axis in LSCC development, which indicated that MSC-AS1 is an attractive biomarker in the LSCC treatment.

Keywords

ATXN7; CTCF; Laryngeal squamous cell cancer; Long noncoding RNA MSC-AS1; YTHDC1.

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