Circular RNA circNHSL1 Contributes to Gastric Cancer Progression Through the miR-149-5p/YWHAZ Axis

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Gastric cancer (GC) poses a significant global health challenge.
• Circular RNA Nance-Horan syndrome-like 1 (circNHSL1) is upregulated in GC, but its functional role remains largely unknown.

Purpose of the Study:

• To elucidate the molecular mechanism and function of circNHSL1 in gastric cancer progression.
• To investigate the potential of circNHSL1 as a therapeutic target for GC.

Main Methods:

• Quantitative PCR and Western blot were used to detect expression levels of circNHSL1, miR-149-5p, and YWHAZ.
• Transwell assays assessed cell migration and invasion.
• Glutamine metabolism was analyzed, and RNA-protein interactions were validated via dual-luciferase reporter and RNA pull-down assays.
• In vivo tumor growth was evaluated using a xenograft model.

Main Results:

• CircNHSL1 expression was elevated in GC cells, tissues, and exosomes.
• Knockdown of circNHSL1 suppressed GC cell migration, invasion, and glutaminolysis.
• CircNHSL1 acts as a sponge for miR-149-5p, influencing YWHAZ expression and promoting GC progression.
• Downregulation of circNHSL1 inhibited tumor growth in vivo.

Conclusions:

• CircNHSL1 knockdown inhibits GC cell migration, invasion, and glutaminolysis in vitro and tumor growth in vivo.
• The circNHSL1/miR-149-5p/YWHAZ axis plays a critical role in GC pathogenesis.
• CircNHSL1 represents a promising therapeutic target for gastric cancer treatment.