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Long Noncoding RNA HITTERS Protects Oral Squamous Cell Carcinoma Cells from Endoplasmic Reticulum Stress-Induced

Chenzhou Wu1, Wen Chen1, Fanyuan Yu2

  • 1State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and Department of Head and Neck Oncology West China Hospital of Stomatology Sichuan University Number 14, Unit 3, Renmin Nan Road Chengdu Sichuan 610041 China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 26, 2020
PubMed

Insights

A novel long noncoding RNA, HITTERS, links endoplasmic reticulum (ER) stress and DNA damage response (DDR) in oral cancer. HITTERS promotes oral squamous cell carcinoma (OSCC) progression and protects against ER stress-induced apoptosis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Long noncoding RNAs (lncRNAs) regulate DNA damage response (DDR) and endoplasmic reticulum (ER) stress.
  • Oral squamous cell carcinoma (OSCC) involves complex molecular pathways.
  • The interplay between ER stress and DDR in OSCC is not fully understood.

Purpose of the Study:

  • To identify novel lncRNAs involved in ER stress in OSCC.
  • To investigate the role of the identified lncRNA in OSCC progression and survival.
  • To elucidate the mechanism linking ER stress and DDR in OSCC.

Main Methods:

  • Transcriptomic analysis of ER stress-induced lncRNAs in OSCC cells.
  • Identification and characterization of the lncRNA HITTERS (HERPUD1 intronic transcript of ER stress).
  • Gain- and loss-of-function studies, in vivo and in vitro experiments, and molecular mechanism investigations.

Main Results:

  • HITTERS was identified as the most significantly upregulated lncRNA under ER stress in OSCC.
  • HITTERS promotes OSCC proliferation and invasion and attenuates ER stress-induced apoptosis.
  • HITTERS functions as an RNA scaffold, promoting MRE11-RAD50-NBS1 complex formation for DNA damage repair.

Conclusions:

  • HITTERS is a novel nucleus-located lncRNA regulated by ATF6, ATF4, XBP1, and DNA methylation.
  • HITTERS expression correlates with OSCC clinicopathological features and prognosis.
  • HITTERS serves as a crucial link between ER stress and DDR in OSCC, offering potential therapeutic targets.
Keywords:
DNA damage responseapoptosisendoplasmic reticulum stresslong noncoding RNAoral squamous cell carcinoma

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