RETRACTED ARTICLE: LncRNA PVT1 triggers Cyto-protective autophagy and promotes pancreatic ductal adenocarcinoma development via the miR-20a-5p/ULK1 Axis

Abstract

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.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0845-6) contains supplementary material, which is available to authorized users.

Long non-coding RNA PVT1 interacts with MYC and its downstream molecules to synergistically promote tumorigenesis

“…Thus, PVT1 may upregulate the expression level of VEGF through inhibiting miR-200b. Moreover, PVT1 may increase the expression of VEGF by inhibiting miR-20a [13,112]. Therefore, PVT1 participates in the downstream angiogenesisrelated signaling pathway of c-Myc and can promote tumor angiogenesis ( Fig.…”

“…Studies have shown that PVT1 is expressed at low levels in normal tissues, while it is highly expressed in various malignant tumors and tumor cell lines, such as gastric cancer, lung cancer, hepatocellular carcinoma, thyroid carcinoma, breast cancer, and pancreatic cancer [7,[9][10][11][12][13][14][15][16]. PVT1 can also serve as a potential predictor of cancer progression and patient prognosis [10,14,15].…”

“…PVT1 can also serve as a potential predictor of cancer progression and patient prognosis [10,14,15]. Most studies have reported that PVT1 can promote proliferation, angiogenesis, apoptosis escape, and participate in DNA rearrangements, which might ultimately promote carcinogenesis [7,10,11,13,17,18]. However, recent studies have shown that PVT1, also a microRNA Host gene, can encode miR-1204, miR-1205, miR-1206, miR-1207-5p, miR-1207-3p, and miR-1208 [7,[19][20][21].…”

Long noncoding RNA RP11‐626G11.3 promotes the progression of glioma through miR‐375‐SP1 axis

“…Notably, recent studies have proven that lncRNAs can act as miRNA sponges to regulate mRNA expression levels 19,20 . LncRNA PVT1 acts as a miR‐20a‐5p sponge to induce cytoprotective autophagy and promote pancreatic ductal adenocarcinoma development by regulating the expression of ULK1 21 . LncRNA MAR1 promotes skeletal muscle differentiation and regeneration via the miR‐487b/Wnt5a axis 13 .…”

“…19,20 LncRNA PVT1 acts as a miR-20a-5p sponge to induce cytoprotective autophagy and promote pancreatic ductal adenocarcinoma development by regulating the expression of ULK1. 21 LncRNA MAR1 promotes skeletal muscle differentiation and regeneration via the miR-487b/Wnt5a axis. 13 Here, the miRcode and starBase v3.0 databases were used to explore the potential miRNAs that interact with lncRNA RP11-626G11.3 and miR-375 has been found.…”