LncRNA SLC16A1-AS1 cooperates with NSUN2 to stabilize GRP78 mRNA via m5C modification in gastric cancer

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• Long noncoding RNAs (lncRNAs) are critical regulators of gene expression and chromatin dynamics.
• Dysregulation of lncRNAs is implicated in various cancers, including gastric cancer (GC).
• The specific roles of lncRNAs in GC pathogenesis are not fully elucidated.

Purpose of the Study:

• To investigate the role of lncRNA solute carrier family 16 member 1 antisense RNA 1 (SLC16A1-AS1) in gastric cancer.
• To elucidate the molecular mechanism by which SLC16A1-AS1 influences GC progression.

Main Methods:

• Integrated RNA sequencing (RNA-seq) for lncRNA profiling in GC.
• Clinical tissue validation and correlation analysis with patient prognosis.
• In vitro and in vivo functional assays (overexpression and knockdown).
• Mechanistic studies involving RNA-protein interactions and mRNA modification analysis (m5C).

Main Results:

• SLC16A1-AS1 was significantly overexpressed in GC tissues and correlated with advanced stage, invasion depth, and poor prognosis.
• SLC16A1-AS1 overexpression promoted GC cell proliferation, while its knockdown inhibited proliferation in vitro and in vivo.
• SLC16A1-AS1 enhanced the m5C modification of GRP78 mRNA by interacting with NSUN2, leading to GRP78 stabilization and increased protein levels.
• GRP78 overexpression rescued the inhibitory effect of SLC16A1-AS1 depletion on GC cell proliferation.

Conclusions:

• SLC16A1-AS1 promotes gastric cancer cell proliferation through NSUN2-mediated m5C modification and stabilization of GRP78 mRNA.
• SLC16A1-AS1 represents a potential diagnostic and therapeutic target for gastric cancer.