Li Xiao-Yu, Sun Jian-Ping, Guo Hao, Fan Xiao-Qing, Zhang Shan-Shan, Wang Bo, Yu Na, Li Qing-Huai
Department of Thyroid and Breast Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Kaohsiung J Med Sci. 2025 Jun;41(6):e70028. doi: 10.1002/kjm2.70028. Epub 2025 Apr 28.
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.
本研究探讨了RASD2（富含纹状体的Ras同源物）在甲状腺癌进展中的作用及其受微小RNA-485-5p的调控。最初通过对公共数据库的生物信息学分析确定了RASD2的差异表达模式。免疫组织化学染色和定量逆转录PCR（qRT-PCR）在临床标本和细胞系中验证了这些发现。通过功能缺失研究对RASD2进行功能表征，检测细胞增殖、侵袭和糖酵解参数。通过Kaplan-Meier分析评估RASD2的预后意义。使用综合生物信息学方法，我们确定微小RNA-485-5p为RASD2的潜在调节因子，并通过分子研究证实了这种相互作用。使用异种移植和肺转移模型评估靶向RASD2的治疗潜力。RASD2在甲状腺癌组织中显著上调，其表达升高与包括淋巴转移、甲状腺外侵犯和晚期TNM分期在内的不良临床病理参数相关。在IHH4和TPC-1细胞中对RASD2进行基因沉默显著损害了它们的恶性表型，表现为增殖、侵袭和糖酵解活性降低。机制上，我们确定微小RNA-485-5p是RASD2的关键负调节因子，其过表达重现了RASD2敲低的肿瘤抑制作用。体内研究进一步验证了抑制RASD2的治疗潜力，显示肿瘤生长和转移负担减轻。我们的研究结果确立了微小RNA-485-5p/RASD2轴是甲状腺癌进展中的关键调节途径，为疾病发病机制和潜在治疗干预提供了新的见解。
