Modulation of RASD2 by miRNA-485-5p Drives Thyroid Cancer Progression and Metastasis

This study investigates the role of RASD2 (Ras Homolog Enriched In Striatum) in thyroid carcinoma progression and its modulation by microRNA-485-5p. Differential RASD2 expression patterns were initially identified through bioinformatic analysis of public databases. Immunohistochemical staining and quantitative reverse transcription PCR (qRT-PCR) validated these findings in clinical specimens and cell lines. Functional characterization of RASD2 was performed through loss-of-function studies, examining cellular proliferation, invasion, and glycolytic parameters. The prognostic significance of RASD2 was evaluated through Kaplan-Meier analysis. Using integrated bioinformatic approaches, we identified miRNA-485-5p as a potential RASD2 regulator and confirmed this interaction through molecular studies. The therapeutic potential of targeting RASD2 was assessed using xenograft and pulmonary metastasis models. RASD2 showed significant upregulation in thyroid cancer tissues, with elevated expression correlating with adverse clinicopathological parameters including lymphatic metastasis, extrathyroidal invasion, and advanced TNM stage. Genetic silencing of RASD2 in IHH4 and TPC-1 cells substantially impaired their malignant phenotypes, manifesting as decreased proliferation, invasion, and glycolytic activity. Mechanistically, we identified miRNA-485-5p as a crucial negative regulator of RASD2, whose overexpression recapitulated the tumor-suppressive effects of RASD2 knockdown. In vivo studies further validated the therapeutic potential of RASD2 inhibition, demonstrating reduced tumor growth and metastatic burden. Our findings establish the miRNA-485-5p/RASD2 axis as a critical regulatory pathway in thyroid cancer progression, offering new insights into disease pathogenesis and potential therapeutic interventions.