Abstract：
Revealing the role of non-coding RNAs (ncRNAs) in inducing dysregulated pathological responses to external signals may identify therapeutic targets for inhibiting the progression of clear cell renal cell carcinoma (ccRCC). Non-coding RNAs belong to a class of RNA molecules that do not encode proteins but possess diverse biological functions, playing essential roles in the occurrence and development of metastatic and proliferative tumors. To investigate the impact of the upstream interaction between miR-142-3p and lncRNA MAGI2-AS3 on the tumor-suppressive activity of the STAM gene, we firstly conducted bioinformatics analysis to predict the upstream miRNAs of STAM and the upstream lncRNAs of the miRNAs through online databases (miRanda, miRDB, TargetScan, LncBase v2), which were further validated by the starBasev2.0 database. Subsequently, multiple experimental techniques were employed to validate these findings, including RT-qPCR, Western blotting, measurement of cellular functional activity, and luciferase reporter assays. Through these experimental methods, we provided compelling evidence regarding the role of miR-142-3p and MAGI2-AS3 in regulating STAM gene expression and functionality, revealing their potential significance in tumor suppression. Our research demonstrates the importance of the MAGI2-AS3/miR-142-3p/STAM signaling pathway axis in ccRCC. MAGI2-AS3 competes for binding with miR-142-3p, resulting in upregulated STAM gene expression. This upregulation inhibits tumor proliferation and metastasis in ccRCC cells. Conversely, overexpression of miR-142-3p or silencing of MAGI2-AS3 promotes tumor behavior, while downregulation of miR-142-3p inhibits the development of ccRCC. Targeting the MAGI2-AS3/miR-142-3p/STAM axis holds promise as a therapeutic strategy for ccRCC treatment.
摘要：
揭示非编码RNA（ncRNA）在诱导外部信号失调的病理反应中的作用可能会确定抑制透明细胞肾细胞癌（ccRCC）进展的治疗靶标。非编码RNA属于一类不编码蛋白质但具有多种生物学功能的RNA分子。在转移和增殖性肿瘤的发生和发展中起着至关重要的作用。为了研究miR-142-3p和lncRNAMAGI2-AS3之间的上游相互作用对STAM基因肿瘤抑制活性的影响，我们首先进行了生物信息学分析，通过在线数据库预测STAM的上游miRNAs和miRNAs的上游lncRNAs(miRanda，miRDB,TargetScan,LncBasev2),starBasev2.0数据库进一步验证。随后，采用了多种实验技术来验证这些发现，包括RT-qPCR，西方印迹,细胞功能活动的测量，和荧光素酶报告基因测定。通过这些实验方法,我们提供了关于miR-142-3p和MAGI2-AS3在调节STAM基因表达和功能中的作用的令人信服的证据，揭示它们在肿瘤抑制中的潜在意义。我们的研究证明了MAGI2-AS3/miR-142-3p/STAM信号通路轴在ccRCC中的重要性。MAGI2-AS3与miR-142-3p竞争结合，导致STAM基因表达上调。这种上调抑制ccRCC细胞中的肿瘤增殖和转移。相反，miR-142-3p的过表达或MAGI2-AS3的沉默促进肿瘤行为，而miR-142-3p的下调抑制ccRCC的发展。靶向MAGI2-AS3/miR-142-3p/STAM轴有望作为ccRCC治疗的治疗策略。
