ArticleCell death & disease2021
A KLF4/PiHL/EZH2/HMGA2 regulatory axis and its function in promoting oxaliplatin-resistance of colorectal cancer.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 80 citations in OpenAlex.
- Krüppel-Like Factor 4, a Hub Gate for Cell Crosstalk in Tumor Microenvironment.Cancer medicine · 2026Review
- DNA, RNA, and histone methylation regulation enzymes and their crosstalk in colorectal carcinogenesis and progression: a review of molecular mechanisms, clinical implications, and future perspectives.Cellular & molecular biology letters · 2025Review
- KLF4 in cancer chemoresistance: molecular mechanisms and therapeutic implications.Discover oncology · 2025Review
- USF1-activated hsa_circ_0076691 induces oxaliplatin resistance via facilitating FGF9 expression in miR-589-3p-dependent manners.Non-coding RNA research · 2025Article
- [High expression of ELFN1 is a prognostic biomarker and promotes proliferation and metastasis of colorectal cancer cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- LncRNA-Protein Interactions: A Key to Deciphering LncRNA Mechanisms.Biomolecules · 2025Review
- Long noncoding RNA GDIL acts as a scaffold for CHAC1 and XRN2 to promote platinum resistance of colorectal cancer through inhibition of glutathione degradation.Cell death & disease · 2025Article
- Treatment of stage IV colorectal cancer: A retrospective cohort study assessing whether failure of first‑line treatment indicates failure of second‑line treatment.Molecular and clinical oncology · 2025Article
- The Role of EZH2 in Initiating Epigenetic Regulation of CRSwNP.Journal of inflammation research · 2025Article
- KLF4: a multifunctional nexus connecting tumor progression and immune regulation.Frontiers in immunology · 2025Review
- THBS2 + cancer-associated fibroblasts promote EMT leading to oxaliplatin resistance via COL8A1-mediated PI3K/AKT activation in colorectal cancer.Molecular cancer · 2024Article
- Epigenetic modifications involving ncRNAs in digestive system cancers: focus on histone modification.Clinical epigenetics · 2024Review
- The emerging role and mechanism of HMGA2 in breast cancer.Journal of cancer research and clinical oncology · 2024Review
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.Frontiers in molecular biosciences · 2024Review
- KLF4 targets RAB26 and decreases 5-FU resistance through inhibiting autophagy in colon cancer.Cancer biology & therapy · 2023Article
- Article
- Exosomal non-coding RNAs: Blueprint in colorectal cancer metastasis and therapeutic targets.Non-coding RNA research · 2023Review
- Current insights into the oncogenic roles of lncRNA LINC00355.Cancer innovation · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Long noncoding RNAs (lncRNAs) have emerged as a new class of regulatory molecules implicated in therapeutic resistance, yet the mechanisms underlying lncRNA-mediated oxaliplatin resistance in colorectal cancer (CRC) are poorly understood. In this study, lncRNA P53 inHibiting LncRNA (PiHL) was shown to be highly induced in oxaliplatin-resistant CRC cells and tumor tissues. In vitro and in vivo models clarified PiHL's role in conferring resistance to oxaliplatin-induced apoptosis. PiHL antagonized chemosensitivity through binding with EZH2, repressing location of EZH2 to HMGA2 promoter, and downregulating methylation of histone H3 lysine 27 (H3K27me3) level in HMGA2 promoter, thus activating HMGA2 expression. Furthermore, HMGA2 upregulation induced by PiHL promotes PI3K/Akt phosphorylation, which resulted in increased oxaliplatin resistance. We also found that transcription factor KLF4 was downregulated in oxaliplatin-resistant cells, and KLF4 negatively regulated PiHL expression by binding to PiHL promoter. In vivo models further demonstrated that treatment of oxaliplatin-resistant CRC with locked nucleic acids targeting PiHL restored oxaliplatin response. Collectively, this study established lncRNA PiHL as a chemoresistance promoter in CRC, and targeting PiHL/EZH2/HMGA2/PI3K/Akt signaling axis represents a novel choice in the investigation of drug resistance.
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