ArticleCell death and differentiation2022
Targeting the miR-34a/LRPPRC/MDR1 axis collapse the chemoresistance in P53 inactive colorectal cancer.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- ER-Localized DeadenylaseExploration (Beijing, China) · 2026Article
- Opportunities in cancer gene therapy: inhibiting MDM2 and restoring p14ARF as a means to activate p53.Molecular and cellular biochemistry · 2026Review
- p53-R280S mutation confers lenvatinib resistance in hepatocellular carcinoma via Bcl-2-mediated anti-apoptotic signaling.Molecular and cellular biochemistry · 2026Article
- Targeting LRPPRC to improve corneal wound healing via augmenting autophagy and suppressing TGF-β/Smad signaling post-alkali burn.Journal of translational medicine · 2026Article
- Targeting LRPPRC lactylation disrupts metabolic-immune crosstalk and restores antitumor immunity in hepatocellular carcinoma.Translational cancer research · 2026Article
- Article
- AT-101 inhibits the proliferation and invasion of tongue squamous carcinoma cells by targeting the miR-21-5p/FDX1 axis.Scientific reports · 2026Article
- Diet-Driven Epigenetic Alterations in Colorectal Cancer: From DNA Methylation and microRNA Expression to Liquid Biopsy Readouts.Biomedicines · 2026Review
- ALDH2 regulates oxaliplatin sensitivity via PDE4B in p53-mutant colorectal cancer.International journal of medical sciences · 2026Article
- Study of ß-catenin signaling pathway modulated by PTHrP in cell and animal colorectal cancer models.Frontiers in oncology · 2026Article
- Clinofibrate Disrupts the SNORA80B/YTHDC1-Driven M6A Modification to Suppress Cholesterol Metabolism and Cisplatin Resistance in ESCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MiR-142-3p targets the CXCL12/WNT/β-catenin pathway to regulate the stemness of breast cancer cells.Scientific reports · 2025Article
- Non-Coding RNAs and cernas: emerging modulators of drug response in colorectal cancer.Molecular biology reports · 2025Review
- The multifaceted role of microRNAs in colorectal cancer: pathogenesis and therapeutic implications.Non-coding RNA research · 2025Review
- Antitumor effects of Dadas Cress (Lepidium sativum var. sativum) on Ehrlich Ascites tumor cells: an in vitro and in vivo study.Journal of molecular histology · 2025Article
- Glycogen stores mediated by the p53-GYS1 feedback circuit engenders platinum resistance in ovarian clear cell carcinoma.Cell death and differentiation · 2025Article
- Article
- Leucyl-tRNA synthetase promotes malignant progression in diffuse large B-cell lymphoma by regulating glycolysis via the LRPPRC/HIF-1α/HK2 axis.Human cell · 2025Article
- The Multifaceted Role of p53 in Cancer Molecular Biology: Insights for Precision Diagnosis and Therapeutic Breakthroughs.Biomolecules · 2025Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P53 mutation is an important cause of chemoresistance in colorectal cancer (CRC). The investigation and identification of the downstream targets and underlying molecular mechanism of chemoresistance induced by P53 abnormalities are therefore of great clinical significance. In this study, we demonstrated and reported for the first time that leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is a key functional downstream factor and therapeutic target for P53 mutation-induced chemoresistance. Due to its RNA binding function, LRPPRC specifically bound to the mRNA of multidrug resistance 1 (MDR1), increasing MDR1 mRNA stability and protein expression. In normal cells, P53 induced by chemotherapy inhibited the expression of LRPPRC via miR-34a and in turn reduced the expression of MDR1. However, chemotherapy-induced P53/miR-34a/LRPPRC/MDR1 signalling pathway activation was lost when P53 was mutated. Additionally, the accumulated LRPPRC and MDR1 promoted drug resistance. Most importantly, gossypol-acetic acid (GAA) was recently reported by our team as the first specific inhibitor of LRPPRC. In CRC cells with P53 mutation, GAA effectively induced degradation of the LRPPRC protein and reduced chemoresistance. Both in vivo and in vitro experiments revealed that combination chemotherapy with GAA and 5-fluorouracil (5FU) yielded improved treatment outcomes. In this study, we reported a novel mechanism and target related to P53-induced drug resistance and provided corresponding interventional strategies for the precision treatment of CRC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.