A new tandem repeat-enriched lncRNA XLOC_008672 promotes gastric carcinogenesis by regulating G3BP1 expression

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Aberrant forkhead box transcription factor 1 (FOXM1) expression is linked to poor prognosis in human cancers.
• The role of long noncoding RNAs (lncRNAs) in tumorigenesis, particularly their interaction with FOXM1, remains largely unexplored.

Purpose of the Study:

• To identify and characterize a novel lncRNA regulated by FOXM1 in gastric cancer (GC).
• To elucidate the functional role and molecular mechanism of the identified lncRNA in GC progression.
• To evaluate the potential of targeting the FOXM1/lncRNA pathway as a therapeutic strategy for GC.

Main Methods:

• LncRNA microarrays were employed to screen differentially expressed lncRNAs in FOXM1-knockdown GC cells.
• Sequence analysis was performed to characterize the identified lncRNA, XLOC_008672.
• In vitro and in vivo functional assays were conducted to determine the role of XLOC_008672 in GC cells.
• Expression levels of XLOC_008672 in GC tissues were analyzed.

Main Results:

• A previously uncharacterized lncRNA, XLOC_008672, containing tandem repetitive sequences, was identified and found to be transcriptionally activated by FOXM1.
• XLOC_008672 expression was significantly elevated in GC tissues and correlated with worse prognosis.
• Mechanistically, XLOC_008672 binds to small nuclear ribonucleoprotein polypeptide A (SNRPA), enhancing Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) mRNA stability, thereby promoting GC cell proliferation and migration.

Conclusions:

• The study identifies XLOC_008672 as a novel oncogenic lncRNA involved in gastric cancer initiation and progression.
• The FOXM1/XLOC_008672/SNRPA/G3BP1 signaling axis represents a potential therapeutic target for gastric cancer treatment.