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

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.