Depletion of the lncRNA RP11-567G11.1 inhibits pancreatic cancer progression
Depletion of the lncRNA RP11-567G11.1 inhibits pancreatic cancer progression
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DOI：
10.1016/j.biopha.2019.108685
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发表时间：
2019-04-01
影响因子：
7.5
通讯作者：
Chou, Jing
中科院分区：
文献类型：
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作者：
Huang, Ranglang;Nie, Wanpin;Chou, Jing
背景：胰腺癌是最致命的恶性肿瘤之一，其5年生存率不到10%。胰腺癌对常规治疗的不良反应，特别是针对癌症干细胞（CSCs），是提高患者生存率的主要障碍。新发现的证据表明，长链非编码RNA (lncRNA) RP11-567G11.1在胰腺癌组织中表达上调，其表达与预后不良有关。本研究旨在阐明RP11-567G11.1影响胰腺癌存活的机制。方法：采用原位杂交技术检测RP11-567G11.1在胰腺癌组织中的表达。我们还构建了RP11-567G11.1敲低细胞模型，并使用CCK8和流式细胞术检测该lncRNA的功能。采用Western blotting和qPCR检测RP11-567G11.1相关因子的表达水平。结果：与非肿瘤组织相比，RP11-567G11.1在低分化胰腺癌组织中的表达明显上调。此外，在胰腺癌细胞中缺失RP11-567G11.1抑制增殖和细胞周期进程，诱导凋亡，抑制干细胞样表型，增加对吉西他滨的敏感性。此外，胰腺癌细胞中RP11-567G11.1的缺失抑制了NOTCH信号通路下游的因子。结论：RP11-567G11.1在胰腺癌中起重要作用。重要的是，RP11-567G11.1的缺失增强了胰腺癌细胞对吉西他滨的敏感性，这表明该lncRNA是胰腺癌治疗的一个有希望的靶点。
Background: Pancreatic cancer is one of the most lethal malignancies, as demonstrated by its 5-year survival rate of less than 10%. The poor response of pancreatic cancer to conventional therapeutics, especially against cancer stem cells (CSCs), is the primary obstacle to improving patient survival. Emerging evidence indicates that the long non-coding RNA (lncRNA) RP11-567G11.1 is up-regulated in pancreatic cancer tissues and that its expression is associated with poor prognosis. This study aimed to elucidate the mechanism by which RP11-567G11.1 influences survival in pancreatic cancer.Methods: We evaluated the expression of RP11-567G11.1 in pancreatic cancer tissues via in situ hybridization. We also constructed RP11-567G11.1 knockdown cell models and used CCK8 and flow cytometry to detect the function of this lncRNA. Western blotting and qPCR were used to detect the expression levels of factors related to RP11-567G11.1.Results: The results illustrated that RP11-567G11.1 was significantly up-regulated in poorly differentiated pancreatic cancer tissues as compared to its expression in non-tumor tissues. Additionally, depletion of RP11-567G11.1 in pancreatic cancer cells inhibited proliferation and cell cycle progression, induced apoptosis, suppressed the stem cell-like phenotype, and increased sensitivity to gemcitabine. Also depletion of RP11-567G11.1 in pancreatic cancer cells inhibited factors downstream of the NOTCH signaling pathway.Conclusion: RP11-567G11.1 plays a crucial role in pancreatic cancer. Importantly, depletion of RP11-567G11.1 boosts the sensitivity of pancreatic cancer cells to gemcitabine, suggesting that this lncRNA is a promising target for pancreatic cancer treatment.