Oncogenic role of LncRNA DLEU2 in thyroid cancer through a NAT10/USP39 regulatory axis.

Thyroid cancer incidence is rapidly increasing worldwide, with many patients’ developing radioiodine-refractory disease that leads to a poor prognosis. Long non-coding RNAs (lncRNAs) are critical regulators of tumor progression. While DLEU2 has been implicated in several cancers, its specific function in thyroid cancer remained undefined. This study aimed to investigate the role of DLEU2 in thyroid cancer progression through its interaction with NAT10 and USP39. We examined DLEU2 expression in 70 paired thyroid cancer and adjacent tissues, and in multiple cell lines using qRT-PCR, finding marked upregulation correlated with higher pathological grade and worse survival. Functional assays demonstrated that silencing DLEU2 significantly reduced cell proliferation, migration, and invasion in vitro, while its overexpression produced the opposite effects. Mechanistically, co-immunoprecipitation confirmed that DLEU2 physically interacts with both NAT10 and USP39, and DLEU2 knockdown specifically decreased their protein levels without affecting mRNA expression, suggesting post-translational regulation. These in vitro findings were further validated in vivo, where tumors from DLEU2-silenced xenografts exhibited significantly smaller volume and weight, accompanied by reduced Ki-67 expression. Overall, this study identifies DLEU2 as an oncogenic lncRNA that promotes thyroid cancer progression through stabilization of NAT10 and USP39, highlighting its potential as both a promising biomarker and therapeutic target for clinical intervention.