Abstract
Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in oncology due to its dismal prognosis and limited therapeutic options. In this study, we investigated the role of miR-301a in facilitating crosstalk between the Hedgehog (Hh) and HIPPO/YAP signaling pathways during the progression of PDAC. Our findings revealed that miR-301a served as a central regulatory node, targeting Gli1 within the Hh pathway and STK4 within the HIPPO/YAP pathway. Immunohistochemical and molecular analyses confirmed dysregulation of pathway components in pancreatic cancer, underscoring the pivotal role of miR-301a. Functional assays demonstrated the impact of miR-301a on cell proliferation and apoptosis, particularly in synergy with TNF-α. Overall, our study elucidated the intricate interplay between the Hh and HIPPO/YAP pathways mediated by miR-301a, providing valuable insights into potential therapeutic strategies for intervening in PDAC.
Keywords:
Gli1; Hedgehog; Hippo/YAP; MST1(STK4); miR-301a.
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Apoptosis
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Carcinoma, Pancreatic Ductal* / genetics
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Carcinoma, Pancreatic Ductal* / metabolism
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Carcinoma, Pancreatic Ductal* / pathology
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Cell Line, Tumor
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Cell Proliferation*
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Gene Expression Regulation, Neoplastic
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Hedgehog Proteins* / genetics
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Hedgehog Proteins* / metabolism
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Hippo Signaling Pathway*
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Humans
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Intracellular Signaling Peptides and Proteins
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MicroRNAs* / genetics
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MicroRNAs* / metabolism
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Pancreatic Neoplasms* / genetics
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Pancreatic Neoplasms* / metabolism
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Pancreatic Neoplasms* / pathology
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Protein Serine-Threonine Kinases* / genetics
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Protein Serine-Threonine Kinases* / metabolism
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Signal Transduction*
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Transcription Factors* / genetics
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Transcription Factors* / metabolism
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YAP-Signaling Proteins / metabolism
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Zinc Finger Protein GLI1 / genetics
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Zinc Finger Protein GLI1 / metabolism
Substances
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MicroRNAs
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Hedgehog Proteins
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Transcription Factors
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Protein Serine-Threonine Kinases
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MIRN301A microRNA, human
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YAP-Signaling Proteins
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Adaptor Proteins, Signal Transducing
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YAP1 protein, human
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Zinc Finger Protein GLI1
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STK4 protein, human
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GLI1 protein, human
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Intracellular Signaling Peptides and Proteins