ArticleFrontiers in oncology2025
LncRNA ZFHX4-AS1 initiates an oncogenic axis involving a ZFHX4/SOX2 positive feedback loop to accelerate glioma progression.
Article in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: The long non-coding RNA ZFHX4-AS1 is a recently identified transcript with an unknown role in glioma. Here, we demonstrate that ZFHX4-AS1 and its neighboring protein-coding gene, ZFHX4, are both significantly upregulated in glioma, and their high expression correlates with poor patient prognosis. Methods: We integrated pan-cancer and glioma transcriptomic datasets from TCGA to assess ZFHX4-AS1 and ZFHX4 expression patterns and their prognostic relevance. We analyzed the expression of ZFHX4-AS1 and its neighboring gene ZFHX4 in human glioma tissues and correlated it with patient prognosis. Functional assays, including cell proliferation, migration, and invasion tests, were conducted Results: Functionally, both ZFHX4-AS1 and ZFHX4 promote glioma cell proliferation, migration, and invasion in vitro and tumor growth Discussion: In conclusion, our study significantly expands upon the understanding of the ZFHX4-AS1 pathway in glioma. We demonstrate that ZFHX4-AS1 initiates an oncogenic signal which is powerfully amplified by a previously unidentified ZFHX4/SOX2 positive feedback loop. We further establish that this entire axis ultimately converges on the activation of the JAK-STAT pathway. This detailed ZFHX4-AS1/ZFHX4/SOX2/JAK-STAT axis represents a promising set of therapeutic targets for glioma treatment.
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