Guo Guangxiu, Dai Sujuan, Chen Qing
Department of Pathology, The People's Hospital of Ganzhou, Gannan, People's Republic of China.
Cancer Manag Res. 2020 May 4;12:3081-3089. doi: 10.2147/CMAR.S237197. eCollection 2020.
Long noncoding RNAs (lncRNAs) are emerging as a class of important biological regulators. lncRNAs participate in diverse biological functions and disease processes, especially those leading to tumorigenesis. In this study, we investigate the role of linc00261 in the pathogenesis of breast cancer.
linc00261 and expression levels were determined in breast cancer tissue and adjacent normal tissue using qRT-PCR. Cell proliferation and migration were analyzed using MTT and transwell assays, respectively. Epithelial-mesenchymal transition markers were examined via Western blotting assay. RNA pull-down was used to examine the interaction between linc00261 and the mRNA transcript.
linc00261 is expressed in lower levels on breast cancer tissues than in para-carcinoma tissues. Reintroduction of linc00261 can inhibit the migration of breast cancer cells and arrest their proliferation. Additionally, linc00261 knockdown is sufficient to cause breast carcinoma tumorigenesis. We also found that linc00261 interacts with mRNA, protecting it from degradation. This protection leads to increased cellular levels of NME1, which functions as suppressor of tumor metastasis.
Taken together, these data demonstrate detailed mechanistic links between the linc00261/NME1 axis and tumorigenesis and show that linc00261 might serve as a novel therapeutic target.
长链非编码RNA(lncRNAs)正成为一类重要的生物调节因子。lncRNAs参与多种生物学功能和疾病过程,尤其是那些导致肿瘤发生的过程。在本研究中,我们探究了linc00261在乳腺癌发病机制中的作用。
采用qRT-PCR检测乳腺癌组织及癌旁正常组织中linc00261的表达水平。分别使用MTT和Transwell实验分析细胞增殖和迁移情况。通过蛋白质免疫印迹实验检测上皮-间质转化标志物。运用RNA下拉实验检测linc00261与NME1 mRNA转录本之间的相互作用。
linc00261在乳腺癌组织中的表达水平低于癌旁组织。重新引入linc00261可抑制乳腺癌细胞的迁移并阻止其增殖。此外,敲低linc00261足以导致乳腺癌的发生。我们还发现linc00261与NME1 mRNA相互作用,保护其不被降解。这种保护导致细胞内NME1水平升高,NME1作为肿瘤转移抑制因子发挥作用。
综上所述,这些数据证明了linc00261/NME1轴与肿瘤发生之间详细的机制联系,并表明linc00261可能成为一个新的治疗靶点。