Long non-coding RNA MIR4435-2HG modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the miR-1252-5p/STAT1
Abstract Cancer stem cells (CSCs) are key drivers of cancer progression and therapeutic resistance. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of CSC properties. The aim of this study was to investigate the role of MIR4435-2HG in regulating CSC characteristics, tumorigenesis,...
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BMC
2025-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06128-8 |
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| author | Baocheng Xie Peishan Wu Hongyu Liu XiangDi Yang Linxuan Huang |
| author_facet | Baocheng Xie Peishan Wu Hongyu Liu XiangDi Yang Linxuan Huang |
| author_sort | Baocheng Xie |
| collection | DOAJ |
| description | Abstract Cancer stem cells (CSCs) are key drivers of cancer progression and therapeutic resistance. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of CSC properties. The aim of this study was to investigate the role of MIR4435-2HG in regulating CSC characteristics, tumorigenesis, and chemoresistance in pancreatic cancer. Functional assays were conducted to evaluate CSC self-renewal, tumorigenic potential, and chemoresistance in pancreatic cancer cells with altered expression of MIR4435-2HG. RNA interference (RNAi) was employed to knock down MIR4435-2HG, and a STAT1 reintroduction model was established to examine downstream signaling pathways. The role of miR-1252-5p as a competing endogenous RNA was also explored. Overexpression of MIR4435-2HG significantly enhanced CSC self-renewal and tumorigenic potential, whereas silencing MIR4435-2HG notably diminished these properties. Mechanistically, MIR4435-2HG promoted STAT1 expression by sponging miR-1252-5p, thereby enhancing CSC stemness and tumorigenesis. Moreover, depletion of MIR4435-2HG sensitized pancreatic cancer cells to gemcitabine-induced growth inhibition and ferroptosis. Reintroduction of STAT1 restored gemcitabine resistance in MIR4435-2HG-deficient cells. Our findings demonstrate that MIR4435-2HG plays a critical role in pancreatic cancer progression by modulating CSC properties and chemoresistance through the MIR4435-2HG/miR-1252-5p/STAT1 axis. Targeting MIR4435-2HG presents a promising therapeutic approach to regulate CSCs and improve the efficacy of chemotherapy in pancreatic cancer. |
| format | Article |
| id | doaj-art-e7012a240c834ffa8996e7a1011786c5 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-e7012a240c834ffa8996e7a1011786c52025-02-09T12:52:30ZengBMCJournal of Translational Medicine1479-58762025-02-0123111710.1186/s12967-025-06128-8Long non-coding RNA MIR4435-2HG modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the miR-1252-5p/STAT1Baocheng Xie0Peishan Wu1Hongyu Liu2XiangDi Yang3Linxuan Huang4Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, Department of Pharmacy, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital)Department of Pharmacology, Guangdong Medical UniversityDepartment of Pharmacology, Guangdong Medical UniversityDongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, Department of Pharmacy, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital)Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan Institute of Clinical Cancer Research, Department of Pharmacy, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital)Abstract Cancer stem cells (CSCs) are key drivers of cancer progression and therapeutic resistance. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of CSC properties. The aim of this study was to investigate the role of MIR4435-2HG in regulating CSC characteristics, tumorigenesis, and chemoresistance in pancreatic cancer. Functional assays were conducted to evaluate CSC self-renewal, tumorigenic potential, and chemoresistance in pancreatic cancer cells with altered expression of MIR4435-2HG. RNA interference (RNAi) was employed to knock down MIR4435-2HG, and a STAT1 reintroduction model was established to examine downstream signaling pathways. The role of miR-1252-5p as a competing endogenous RNA was also explored. Overexpression of MIR4435-2HG significantly enhanced CSC self-renewal and tumorigenic potential, whereas silencing MIR4435-2HG notably diminished these properties. Mechanistically, MIR4435-2HG promoted STAT1 expression by sponging miR-1252-5p, thereby enhancing CSC stemness and tumorigenesis. Moreover, depletion of MIR4435-2HG sensitized pancreatic cancer cells to gemcitabine-induced growth inhibition and ferroptosis. Reintroduction of STAT1 restored gemcitabine resistance in MIR4435-2HG-deficient cells. Our findings demonstrate that MIR4435-2HG plays a critical role in pancreatic cancer progression by modulating CSC properties and chemoresistance through the MIR4435-2HG/miR-1252-5p/STAT1 axis. Targeting MIR4435-2HG presents a promising therapeutic approach to regulate CSCs and improve the efficacy of chemotherapy in pancreatic cancer.https://doi.org/10.1186/s12967-025-06128-8MIR4435-2HGPancreatic cancerCancer stem cellsFerroptosisChemosensitivity |
| spellingShingle | Baocheng Xie Peishan Wu Hongyu Liu XiangDi Yang Linxuan Huang Long non-coding RNA MIR4435-2HG modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the miR-1252-5p/STAT1 Journal of Translational Medicine MIR4435-2HG Pancreatic cancer Cancer stem cells Ferroptosis Chemosensitivity |
| title | Long non-coding RNA MIR4435-2HG modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the miR-1252-5p/STAT1 |
| title_full | Long non-coding RNA MIR4435-2HG modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the miR-1252-5p/STAT1 |
| title_fullStr | Long non-coding RNA MIR4435-2HG modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the miR-1252-5p/STAT1 |
| title_full_unstemmed | Long non-coding RNA MIR4435-2HG modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the miR-1252-5p/STAT1 |
| title_short | Long non-coding RNA MIR4435-2HG modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the miR-1252-5p/STAT1 |
| title_sort | long non coding rna mir4435 2hg modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the mir 1252 5p stat1 |
| topic | MIR4435-2HG Pancreatic cancer Cancer stem cells Ferroptosis Chemosensitivity |
| url | https://doi.org/10.1186/s12967-025-06128-8 |
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