Knockdown of lncRNA BLACAT1 enhances radiosensitivity of head and neck squamous cell carcinoma cells by regulating PSEN1

Br J Radiol. 2020 Apr;93(1108):20190154. doi: 10.1259/bjr.20190154. Epub 2020 Feb 12.

Abstract

Objective: This work focused on the function role and underlying mechanism of BLACAT1 in regulating the radiosensitivity of head and neck squamous cell carcinoma (HNSCC) cells via PSEN1.

Methods: BLACAT1 and PSEN1 expression in HNSCC tissues and cells were measured by qRT-PCR. Kaplan-Meier method and Spearman's correlation analysis determined the prognostic roles and association of BLCAT1 and PSEN1 in HNSCC. The impacts of BLACAT1 and PSEN1, alone and in combination, on radiosensitivity of HNSCC cells were separately assessed through CCK-8, colony formation, flow cytometry, western blot and γH2AX foci staining assays.

Results: Our study disclosed that BLACAT1 and PSEN1 were both in association with poor prognosis and radioresistance of HNSCC cells. BLACAT1 knockdown improved the radiosensitivity of HNSCC cells by changing cellular activities containing repressed cell viability, accelerated cell apoptosis, induced cell cycle arrest, and stimulated DNA damage response. Further, we found that PSEN1 was positively correlated with BLACAT1. Rescue assays confirmed that BLACAT1 regulated the radiosensitivity of HNSCC cells by modulating PSEN1.

Conclusion: We revealed that BLACAT1 knockdown enhanced radioresistance of HNSCC cells via regulating PSEN1, exposing the probable target role of BLACAT1 in HNSCC.

Advances in knowledge: This was the first time that the pivotal role of BLACAT1 was investigated in HNSCC, which provided a novel therapeutic direction for HNSCC patients.

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Survival / genetics
  • DNA Damage
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Hypopharyngeal Neoplasms / genetics
  • Hypopharyngeal Neoplasms / radiotherapy
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / radiotherapy
  • Male
  • Neoplasm Proteins / metabolism
  • Oropharyngeal Neoplasms / genetics
  • Oropharyngeal Neoplasms / radiotherapy
  • Presenilin-1 / metabolism*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Radiation Tolerance / genetics*
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / radiotherapy
  • Up-Regulation

Substances

  • Neoplasm Proteins
  • PSEN1 protein, human
  • Presenilin-1
  • RNA, Long Noncoding
  • long noncoding RNA BLACAT1, human