ArticleMolecular cancer2020
LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/β-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes.
Article in Molecular cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 papers, 1 of them a synthesis that pooled it.
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229 citing papers in PubMed, 1 synthesis or guideline pooled it, 413 citations in OpenAlex.
- Risk SNP in a transcript of RP11-638I2.4 increases lncRNA-YY1 interaction and pancreatic cancer susceptibility.Archives of toxicology · 2023Pooled it
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- Transcriptomic profiling reveals autophagy-associated programs and prognostic biomarkers in anoikis-resistant pancreatic cancer cells.BMC cancer · 2026Article
- Phosphorylated STYK1 Promotes Gemcitabine Resistance via Autophagy-Mediated Cancer Stemness in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Systems biology of Wnt signaling in glioma chemotherapy resistance: Integrating multi-omics mechanisms and emerging therapeutic vulnerabilities (Review).Oncology letters · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT.Nature biotechnology · 2026Article
- Mechanism of lncRNA PLACT1 in regulating the proliferation of pancreatic adenocarcinoma cells through the KLF2/KIAA1522 axis.Histology and histopathology · 2026Article
- Targeting Autophagy to Overcome Chemoresistance and Immune Resistance in Triple-Negative Breast Cancer.Cancers · 2026Review
- The ATG14: multi-layer autophagy control and an emerging therapeutic target in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- Research progress of plant-derived chemical compounds for overcoming pancreatic cancer drug resistance.World journal of gastroenterology · 2026Review
- Role of cuproptosis in digestive system tumors (Review).International journal of molecular medicine · 2026Review
- Salidroside Mitigates Cerebral Ischemic Injury via Modulation of the PVT1/miR-384-5p Regulatory Axis.Applied biochemistry and biotechnology · 2026Article
- LncRNA PVT1 in human cancers: genomic complexity, isoforms, functional elements, mechanism of action, subcellular localization and possible role as a therapeutic target.Molecular cancer · 2026Review
- tRNA mMolecular cancer · 2026Article
- ABHD11-AS1 Suppresses Colorectal Cancer Progression by Disrupting EIF4E-mediated POU2F1 Ubiquitination.International journal of biological sciences · 2026Article
- Unraveling the Predictive Value ofStem cells international · 2026Article
- Long non-coding RNAs: Emerging regulators of invasion and metastasis in pancreatic cancer.Journal of advanced research · 2025Review
- Article
- A long non-coding RNA SCAMP1 induces pancreatic ductal adenocarcinoma progression through miR-106a-5p/AGK signaling.Clinical and experimental medicine · 2025Article
169 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic cancer is one of the most lethal malignancies and has an extremely poor diagnosis and prognosis. The development of resistance to gemcitabine is still a major challenge. The long noncoding RNA PVT1 was reported to be involved in carcinogenesis and chemoresistance; however, the mechanism by which PVT1 regulates the sensitivity of pancreatic cancer to gemcitabine remains poorly understood.
methodsThe viability of pancreatic cancer cells was assessed by MTT assay in vitro and xenograft tumor formation assay in vivo. The expression levels of PVT1 and miR-619-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting analysis and qRT-PCR were performed to assess the protein and mRNA levels of Pygo2 and ATG14, respectively. Autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of PVT1 were further investigated by gain- and loss-of-function assays in vitro.
resultsIn the present study, we demonstrated that PVT1 was up-regulated in gemcitabine-resistant pancreatic cancer cell lines. Gain- and loss-of-function assays revealed that PVT1 impaired sensitivity to gemcitabine in vitro and in vivo. We further found that PVT1 up-regulated the expression of both Pygo2 and ATG14 and thus regulated Wnt/β-catenin signaling and autophagic activity to overcome gemcitabine resistance through sponging miR-619-5p. Moreover, we discovered three TCF/LEF binding elements (TBEs) in the promoter region of PVT1, and activation of Wnt/β-catenin signaling mediated by the up-regulation of Pygo2 increased PVT1 expression by direct binding to the TBE region. Furthermore, PVT1 was discovered to interact with ATG14, thus promoting assembly of the autophagy specific complex I (PtdIns3K-C1) and ATG14-dependent class III PtdIns3K activity.
conclusionsThese data indicate that PVT1 plays a critical role in the sensitivity of pancreatic cancer to gemcitabine and highlight its potential as a valuable target for pancreatic cancer therapy.
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