Long Non-coding RNA TPRG1-AS1 Interacts With CLTC in Liver Cancer Cells

Sung Ung Moon1, Masaud Shah1, Trinh Thanh Thao1

  • 1Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.

Anticancer Research
|October 30, 2024
PubMed
Abstract

Insights

Long non-coding RNA TPRG1-AS1 directly interacts with Clathrin Heavy Chain (CLTC) to suppress liver cancer growth by inhibiting Epidermal Growth Factor (EGF) signaling.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
  • Some lncRNAs function as tumor suppressors, inhibiting tumor progression.
  • The specific mechanisms of lncRNA-mediated tumor suppression are under active investigation.

Purpose of the Study:

  • To investigate the tumor-suppressive mechanism of lncRNA TPRG1-AS1.
  • To elucidate the direct interaction between TPRG1-AS1 and Clathrin Heavy Chain (CLTC).
  • To determine the role of this interaction in the Epidermal Growth Factor (EGF) signaling pathway.

Main Methods:

  • RNA pulldown and RNA immunoprecipitation (RIP)-qPCR to confirm TPRG1-AS1 and CLTC interaction.
  • Cell viability, sphere formation, and invasion assays to assess phenotypic changes.
  • Immunoblotting and immunocytochemistry to confirm the underlying molecular mechanisms.
  • Custom HEX probe assay to verify binding and signaling suppression.

Main Results:

  • TPRG1-AS1 directly interacts with CLTC.
  • Overexpression of TPRG1-AS1 (TPRG1-AS1oe) suppressed EGF downstream signaling, including MAPK8 and MAPK14.
  • This interaction led to reduced cell viability, sphere formation, and invasion in liver cancer cells.
  • TPRG1-AS1oe binding to CLTC attenuated EGF signaling.

Conclusions:

  • A novel regulatory axis involving TPRG1-AS1 and CLTC was identified.
  • TPRG1-AS1 interacts with CLTC to attenuate EGF downstream signaling, specifically MAPK8 and MAPK14 pathways.
  • This interaction contributes to the tumor-suppressive effects observed in liver cancer cells.