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DHRS4-AS1 regulate gastric cancer apoptosis and cell proliferation by destabilizing DHX9 and inhibited the

Lei Xiao1,2,3, Yang Zhang1,2,3, Qingqing Luo4

  • 1Department of General Surgery, Xiangya Hospital of Central South University, Xiangya Road No. 87, Kaifu District, Changsha, 410000, Hunan Province, China.

Cancer Cell International
|December 2, 2023
PubMed

Insights

Long non-coding RNA DHRS4-AS1 suppresses gastric cancer (GC) by inhibiting proliferation and promoting apoptosis. It targets DHX9, reducing tumor growth and improving patient prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gastric cancer (GC) is a leading cause of cancer mortality, characterized by uncontrolled cell proliferation and resistance to apoptosis.
  • The precise molecular mechanisms driving GC progression and survival remain incompletely understood.
  • Identifying novel molecular players is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the role of long non-coding RNA DHRS4-AS1 in gastric cancer.
  • To elucidate the molecular mechanisms by which DHRS4-AS1 influences GC cell proliferation and apoptosis.
  • To evaluate DHRS4-AS1 as a potential diagnostic biomarker and therapeutic target for GC.

Main Methods:

  • Analysis of DHRS4-AS1 expression in GC tissues and databases (GEO).
  • In vitro and in vivo assays to assess the impact of DHRS4-AS1 on GC cell proliferation and apoptosis.
  • Molecular experiments to identify DHRS4-AS1 interacting proteins (DHX9, MDM2, ILF3) and signaling pathways (NF-kB).

Main Results:

  • DHRS4-AS1 was significantly downregulated in GC tissues and correlated with tumor size, advanced stage, and poor prognosis.
  • DHRS4-AS1 overexpression inhibited GC cell proliferation and induced apoptosis both in vitro and in vivo.
  • DHRS4-AS1 facilitates DHX9 degradation via MDM2 recruitment and inhibits DHX9/ILF3-mediated NF-kB activation.

Conclusions:

  • LncRNA DHRS4-AS1 acts as a tumor suppressor in gastric cancer.
  • DHRS4-AS1 exerts its function by targeting DHX9 and modulating the NF-kB signaling pathway.
  • DHRS4-AS1 represents a promising biomarker for GC diagnosis and a potential therapeutic target.
Keywords:
DHRS4-AS1DHX9Gastric cancerILF3NF-κB signaling pathway

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