长链非编码RNA RP5-821D11.7促进胶质瘤和胶质瘤干细胞样细胞的增殖、迁移和上皮-间质转化

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摘要

长链非编码RNA (Long noncoding RNA, lncRNA)是近年来发现的一种重要的调控分子,它与许多细胞功能有关。研究表明,lncRNA异常表达并参与胶质瘤的进展和发生。本研究鉴定了一种与胶质瘤、胶质瘤干细胞样细胞(GSCs)相关的新型lncRNA,并揭示了它们的潜在功能。在筛选lncRNA的过程中,我们发现与胶质瘤细胞相比,lncRNA RP5-821D11.7 (lncRNA- rp5)在GSCs中过表达。构建慢病毒介导的lncRNA-RP5 shRNA并转染胶质瘤细胞。将转染后的稳定胶质瘤细胞移植到裸鼠体内,观察肿瘤生长情况。lncRNA-RP5敲低可通过激活Wnt/β-catenin通路显著抑制细胞增殖、迁移并减少上皮-间质转化(EMT)。此外,lncRNA RP5敲低可通过内质网应激促进细胞凋亡。因此,本研究可能提供更好的理解和证明lncRNA-RP5可能是胶质瘤的潜在治疗靶点。
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Long non-coding RNA RP5-821D11.7 promotes proliferation, migration, and epithelial-mesenchymal transition in glioma and glioma stem-like cells
Long noncoding RNA (lncRNA) has been recently revealed as a main regulatory molecule, implicating many cellular functions. Studies showed that lncRNA is abnormally expressed and involved in the progression and tumorigenesis of glioma. The present study identified a novel lncRNA associated with glioma, glioma stem-like cells (GSCs) and then revealed their potential functions. During the screening of lncRNAs, we found lncRNA RP5-821D11.7 (lncRNA-RP5) overexpress in GSCs compared to glioma cells. Lentivirus-mediated shRNA for lncRNA-RP5 was constructed and transfected into glioma cells. Transfected stable glioma cells were transplanted into nude mice and tumor growth was determined. Knockdown of lncRNA-RP5 significantly inhibits proliferation, migration and reduces epithelial-mesenchymal transition (EMT) by activating the Wnt/β-catenin pathway. Additionally, the results showed that lncRNA RP5 knockdown enhances cell apoptosis through endoplasmic reticulum stress. Therefore, this study may provide a better understanding and demonstrates that lncRNA-RP5 may be a potential therapeutic target in glioma.
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