ArticleCell death & disease2022
Glucocorticoid-induced microRNA-378 signaling mediates the progression of pancreatic cancer by enhancing autophagy.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Endogenous glucocorticoids and glucocorticoid receptor signaling: Dual regulators of PD-1/PD-L1 immunotherapy efficacy in the tumor microenvironment.Chinese medical journal · 2026Review
- Dexamethasone Promotes Autophagy Dependent Ferroptosis of Placental Trophoblast Cells Through GRα.Journal of cellular and molecular medicine · 2025Article
- The Src family kinase inhibitor drug Dasatinib and glucocorticoids display synergistic activity against tongue squamous cell carcinoma and reduce MET kinase activity.Cell communication and signaling : CCS · 2025Article
- Melanophilin-induced primary cilia promote pancreatic cancer metastasis.Cell death & disease · 2025Article
- Article
- Metformin Inhibits the Progression of Pancreatic Cancer Through Regulating miR-378a-3p/VEGFA/RGC-32 Axis.Cancer medicine · 2024Article
- Non-Coding RNAs and Innate Immune Responses in Cancer.Biomedicines · 2024Review
- ECM1 and KRT6A are involved in tumor progression and chemoresistance in the effect of dexamethasone on pancreatic cancer.Cancer science · 2024Article
- Advances in applications of artificial intelligence algorithms for cancer-related miRNA research.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- MicroRNAs in pancreatic cancer drug resistance: mechanisms and therapeutic potential.Frontiers in cell and developmental biology · 2024Review
- Deciphering the role of NcRNAs in Pancreatic Cancer immune evasion and drug resistance: a new perspective for targeted therapy.Frontiers in immunology · 2024Review
- Possible Participation of Adenine Nucleotide Translocase ANT1 in the Cytotoxic Action of Progestins, Glucocorticoids, and Diclofenac on Tumor Cells.Pharmaceutics · 2023Article
- Upregulated miR‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT‑1/ALDOA/PKM2 axis in esophageal carcinoma.Oncology letters · 2023Article
- LncRNA FAM83A-AS1 promotes epithelial-mesenchymal transition of pancreatic cancer cells via Hippo pathway.Cell cycle (Georgetown, Tex.) · 2023Article
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoids (GCs) are widely used in tumor therapy to reduce tumor growth, inflammation, edema, and other side effects. Controversially, GCs may also cause the progression of highly aggressive pancreatic ductal adenocarcinoma (PDAC). Because microRNA (miR) and autophagy signaling support the invasive growth of PDAC, we asked whether these mechanisms may be targeted by GCs. Six established human PDAC cell lines, tissue from patients who received GC medication (n = 35) prior to surgery, or not (n = 35), and tumor xenografts were examined by RT‒qPCR, transmission electron microscopy (TEM), monodansylcadaverine (MDC) staining, immunohistochemistry, in situ hybridization, gene array and Kaplan‒Meier analysis with bioinformatics, and MTT, western blot, colony, spheroid, migration, and invasion assays. We found that various GCs, including dexamethasone (DEX), induced typical features of macroautophagy with the appearance of autolysosomes, enhanced LC3-II, decreased SQSTM1/p62 expression and induced epithelial-mesenchymal transition (EMT) and gemcitabine resistance. The GC receptor (GR) antagonist mifepristone (RU486) counteracted DEX-induced autophagy features, suggesting that the GC-GR complex is involved in the induction of autophagy. The autophagy-related miR-378i and miR-378a-3p were selected as the top upregulated candidates, and their high expression in PDAC patient tissue correlated with low survival. siRNA-mediated downregulation of miR-378 inhibited DEX-induced autophagy, and tumor progression. Bioinformatics confirmed the contribution of miR-378 to the regulation of signaling networks involved in GC-induced autophagy and tumor progression. The construction of a molecular docking model revealed stable binding of miR-378 to the DEX-GR complex, suggesting direct regulation. These substantial, novel, in-depth data reveal that GCs favor autophagy-mediated cancer progression by inducing miR-378 and GR binding and implicate GR and miR-378 as new therapeutic targets.
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