Targeted modulation of IGFL2-AS1 reveals its translational potential in cervical adenocarcinoma

Cervical cancer remains a leading cause of mortality among women, particularly in low- and middle-income countries. Despite distinct prognoses and clinical outcomes between its main histological subtypes, squamous cell carcinoma (SCC) and adenocarcinoma (ADC), current treatment regimens remain largely similar, creating an urgent need for targeted therapeutic strategies based on molecular distinctions. To address this gap, the long noncoding RNA IGFL2-AS1 was investigated as a potential prognostic biomarker and therapeutic target in cervical adenocarcinoma. A translational approach was employed that integrated patient transcriptome data, in silico analysis from public databases, and in vitro validation. Using CRISPR/dCas9 technology, IGFL2-AS1 expression was modulated in HeLa (ADC) and SiHa (SCC) cell lines to assess its impact on cellular characteristics associated with tumorigenesis. In silico analysis revealed that IGFL2-AS1 expression was significantly reduced in ADC compared to SCC, and its low expression was consistently linked to poorer ADC prognosis and decreased patient survival. Notably, overexpression of IGFL2-AS1 in HeLa cells significantly reduced cell proliferation, migration, clonogenic survival, and enhanced sensitivity to cisplatin and doxorubicin. Conversely, IGFL2-AS1 repression in SiHa cells yielded no significant phenotypic changes, suggesting a context-dependent mechanism. IGFL2-AS1 is identified as a histological subtype-specific prognostic biomarker and promising therapeutic target for cervical adenocarcinoma.