Bibliographic Details
| Title: |
Long non-coding RNA MIR4435-2HG modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the miR-1252-5p/STAT1 |
| Authors: |
Baocheng Xie, Peishan Wu, Hongyu Liu, XiangDi Yang, Linxuan Huang |
| Source: |
Journal of Translational Medicine, Vol 23, Iss 1, Pp 1-17 (2025) |
| Publisher Information: |
BMC, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
MIR4435-2HG, Pancreatic cancer, Cancer stem cells, Ferroptosis, Chemosensitivity, Medicine |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1479-5876 |
| Relation: |
https://doaj.org/toc/1479-5876 |
| DOI: |
10.1186/s12967-025-06128-8 |
| Access URL: |
https://doaj.org/article/e7012a240c834ffa8996e7a1011786c5 |
| Accession Number: |
edsdoj.7012a240c834ffa8996e7a1011786c5 |
| Database: |
Directory of Open Access Journals |
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