FOXP4-AS1 suppresses papillary thyroid carcinoma progression by binding to Lactate Dehydrogenase A and suppressing its expression, with implications for metabolic-targeted therapy.

Although FOXP4-AS1 exerts oncogenic effects in multiple cancers, this study reveals that it suppresses PTC progression. A series of experiments demonstrate that overexpression of FOXP4-AS1 inhibits PTC cell proliferation, migration, and invasion, whereas its knockdown promotes these malignant phenotypes and enhances tumorigenesis in nude mice. FOXP4-AS1 is distributed in both the nucleus and cytoplasm, enriched in the aerobic glycolysis pathway, and binds to Lactate Dehydrogenase A (LDHA)-a key enzyme in aerobic glycolysis with known links to tumor metabolic microenvironment. LDHA was primarily localized in the cytoplasm, and its downregulation suppressed the malignant behavior of PTC cells. Further mechanistic investigations reveal that knockdown of FOXP4-AS1 increases LDHA expression, and additional inhibition of LDHA partially reverses the pro-tumor effects induced by FOXP4-AS1 silencing. In conclusion, this study identifies FOXP4-AS1 as a tumor suppressor in PTC and elucidates the regulatory mechanism of the FOXP4-AS1/LDHA axis by which FOXP4-AS1 represses LDHA expression to attenuate aerobic glycolysis, providing novel insights into the mechanisms of PTC progression and potential therapeutic targets and diagnostic biomarkers relevant to metabolic modulation in PTC.