The role of CSTF2 in gastric cancer: implications for therapy

Gastric cancer is a fatal malignancy that is frequently diagnosed at an advanced stage worldwide, and current treatments are limited. The RNA-binding protein CSTF2 is associated with the prognosis of many cancers, but the role it plays in gastric cancer remains unknown.

We collected tissues of gastric cancer and adjacent ones paired adjacent non-tumor tissues at the First Affiliated Hospital of Anhui Medical University. CSTF2 expression was initially detected using immunohistochemistry and Western blotting, and its association with clinicopathological features was assessed. Knockdown of CSTF2 in gastric carcinoma cell models was conducted to examine the effect on cell proliferation, migration, and invasion. The mRNA stability of downstream targets was assessed by actinomycin D assay. Further RNA sequencing analysis revealed the downstream influential genes of CSTF2, especially TGM2. Afterwards, the function of TGM2 and its interactions with CSTF2 were further verified.

The production of CSTF2 was markedly higher in gastric cancer tissues compared to adjacent noncancerous tissues and showed a strong correlation with poor patient prognosis. CSTF2 inhibition significantly suppressed gastric cancer cell growth, proliferation, migration, and invasion. Mechanistically, CSTF2 knockdown accelerated the decay of TGM2 mRNA, indicating that CSTF2 post-transcriptionally stabilizes TGM2 transcripts. Further gene expression analysis revealed that TGM2 might serve as a key downstream effector of CSTF2. Ectopic expression of TGM2 partially rescued the inhibitory effect of CSTF2 deficiency on cell proliferation and colony formation.

CSTF2 promotes gastric cancer progression by post-transcriptionally stabilizing TGM2 mRNA, and its overexpression is closely related to poor prognosis. The elucidated CSTF2-TGM2 regulatory axis may offer a promising and innovative therapeutic target for gastric carcinoma treatment.