SNHG15-mediated feedback loop interplays with HNRNPA1/SLC7A11/GPX4 pathway to promote gastric cancer progression

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Long noncoding RNAs (lncRNAs) are implicated in gastric cancer (GC) initiation and progression.
• The specific role and regulatory mechanisms of lncRNA SNHG15 in GC remain largely uncharacterized.
• Understanding SNHG15's involvement in ferroptosis is crucial for novel therapeutic strategies.

Purpose of the Study:

• To investigate the biological functions of SNHG15 in gastric cancer.
• To elucidate the molecular mechanisms underlying SNHG15's role in GC progression and ferroptosis.
• To identify SNHG15 as a potential therapeutic target for gastric cancer.

Main Methods:

• RNA-sequencing (RNA-seq) data analysis of GC tissues (cohort and TCGA).
• Quantitative real-time PCR (qRT-PCR) for SNHG15 validation.
• In vitro and in vivo gain- and loss-of-function assays.
• Mechanistic studies involving transcription factors (E2F1, MYC), microRNA sponging (miR-24-3p), RNA-binding proteins (HNRNPA1), and ferroptosis markers (SLC7A11, GPX4).

Main Results:

• SNHG15 is highly expressed in GC and correlates with advanced stage and poor prognosis.
• SNHG15 promotes GC cell growth, migration, and invasion in vitro and in vivo.
• SNHG15 expression is upregulated by oncogenic transcription factors E2F1 and MYC.
• SNHG15 inhibits ferroptosis by stabilizing SLC7A11 via HNRNPA1, modulating the SLC7A11/GPX4 axis.

Conclusions:

• SNHG15 acts as an oncogenic lncRNA in gastric cancer, driven by E2F1 and MYC.
• SNHG15 regulates ferroptosis through an HNRNPA1-dependent mechanism involving SLC7A11/GPX4.
• SNHG15 represents a promising therapeutic target for gastric cancer treatment.