LncRNA PVT1 triggers Cyto-protective autophagy and promotes pancreatic ductal adenocarcinoma development via the miR-20a-5p/ULK1 Axis.
LncRNA PVT1 triggers Cyto-protective autophagy and promotes pancreatic ductal adenocarcinoma development via the miR-20a-5p/ULK1 Axis.
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LncRNA PVT1 通过 miR-20a-5p/ULK1 轴触发细胞保护性自噬并促进胰腺导管腺癌的发展
DOI：
10.1186/s12943-018-0845-6
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发表时间：
2018-07-12
期刊：
影响因子：
37.3
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Huang F;Chen W;Peng J;Li Y;Zhuang Y;Zhu Z;Shao C;Yang W;Yao H;Zhang S
背景自噬缺陷被认为是包括癌症在内的许多疾病的致病因素。人浆细胞瘤变异易位1(PVT1)是一种长非编码的致癌RNA，已被认为是胰腺癌预后的生物标志物，但PVT1在胰腺癌自噬调节中的作用尚不清楚。Western印迹或qRT-PCR检测ULK1蛋白或mRNA的表达水平。通过在共聚焦显微镜下检测自噬通量和在透射电子显微镜下观察自噬空泡来研究自噬。通过功能获得和功能缺失分析确定PVT1在自噬和PDA发育中的生物学作用。结果我们发现PVT1在PDA癌组织中的表达水平与ULK1蛋白的水平平行。PVT1通过在体外和体内靶向ULK1促进细胞保护性自噬和细胞生长。此外，PVT1高表达与预后不良有关。结论PVT1/miR-20a-5p/ULK1/ULK1/自噬通路调控胰腺癌的发生发展，可能成为胰腺癌治疗的新靶点。
BackgroundDefective autophagy is thought to contribute to the pathogenesis of many diseases, including cancer. Human plasmacytoma variant translocation 1 (PVT1) is an oncogenic long non-coding RNA that has been identified as a prognostic biomarker in pancreatic ductal adenocarcinoma, but how PVT1 operates in the regulation of autophagy in pancreatic ductal adenocarcinoma (PDA) is unclear.MethodsPVT1 expression level was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and hybridization in situ (ISH). Western blot or qRT-PCR was performed to assess the ULK1 protein or mRNA level. Autophagy was explored via autophagic flux detection under a confocal microscope and autophagic vacuoles investigation under a transmission electron microscopy (TEM). The biological role of PVT1 in autophagy and PDA development was determined by gain-of-function and loss-of-function assays.ResultsWe found that PVT1 levels paralleled those of ULK1 protein in PDA cancer tissues. PVT1 promoted cyto-protective autophagy and cell growth by targeting ULK1 both in vitro and in vivo. Moreover, high PVT1 expression was associated with poor prognosis. Furthermore, we found that PVT1 acted as sponge to regulate miR-20a-5p and thus affected ULK1 expression and the development of pancreatic ductal adenocarcinoma.ConclusionsThe present study demonstrates that the “PVT1/miR-20a-5p/ULK1/autophagy” pathway modulates the development of pancreatic ductal adenocarcinoma and may be a novel target for developing therapeutic strategies for pancreatic ductal adenocarcinoma.
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8.8
作者：
Takahashi, Y.;Sawada, G.;Kurashige, J.;Uchi, R.;Matsumura, T.;Ueo, H.;Takano, Y.;Eguchi, H.;Sudo, T.;Sugimachi, K.;Yamamoto, H.;Doki, Y.;Mori, M.;Mimori, K.
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影响因子：
64.5
作者：
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作者：
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