ArticleMolecular therapy. Nucleic acids2015
Concurrent Targeting of KRAS and AKT by MiR-4689 Is a Novel Treatment Against Mutant KRAS Colorectal Cancer.
Article in Molecular therapy. Nucleic acids, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 95 citations in OpenAlex.
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- Drug resistance mechanisms in cancers: Execution of pro-survival strategies.Journal of biomedical research · 2024Article
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- Karanjin, A Promising Bioactive Compound Possessing Anti-cancer Activity against Experimental Model of Non-small Cell Lung Cancer Cells.Anti-cancer agents in medicinal chemistry · 2024Article
- Role of microRNA in colorectal carcinoma (CRC): a narrative review.Annals of medicine and surgery (2012) · 2024Review
- Stage-specific treatment of colorectal cancer: A microRNA-nanocomposite approach.Journal of pharmaceutical analysis · 2023Review
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- Super Carbonate Apatite-miR-497a-5p Complex Is a Promising Therapeutic Option against Inflammatory Bowel Disease.Pharmaceuticals (Basel, Switzerland) · 2023Article
- KRT13 is upregulated in pancreatic cancer stem-like cells and associated with radioresistance.Journal of radiation research · 2023Article
- Hypoxia-induced long non-coding RNA LINC00460 promotes p53 mediated proliferation and metastasis of pancreatic cancer by regulating the miR-4689/UBE2V1 axis and sequestering USP10.International journal of medical sciences · 2023Article
- Regulatory miRNAs in cancer cell recovery from therapy exposure and its implications as a novel therapeutic strategy for preventing disease recurrence.The Enzymes · 2023Article
- Promotion or remission: a role of noncoding RNAs in colorectal cancer resistance to anti-EGFR therapy.Cell communication and signaling : CCS · 2022Review
- MicroRNAs and Their Big Therapeutic Impacts: Delivery Strategies for Cancer Intervention.Cells · 2022Review
- MicroRNAs as Innovative Biomarkers for Inflammatory Bowel Disease and Prediction of Colorectal Cancer.International journal of molecular sciences · 2022Review
- Nanomedicine for the Delivery of RNA in Cancer.Cancers · 2022Review
- Interplay between K-RAS and miRNAs.Trends in cancer · 2022Review
- Functional assessment of miR‑1291 in colon cancer cells.International journal of oncology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KRAS mutations are a major cause of drug resistance to molecular-targeted therapies. Aberrant epidermal growth factor receptor (EGFR) signaling may cause dysregulation of microRNA (miRNA) and gene regulatory networks, which leads to cancer initiation and progression. To address the functional relevance of miRNAs in mutant KRAS cancers, we transfected exogenous KRAS(G12V) into human embryonic kidney 293 and MRC5 cells with wild-type KRAS and BRAF genes, and we comprehensively profiled the dysregulated miRNAs. The result showed that mature miRNA oligonucleotide (miR)-4689, one of the significantly down-regulated miRNAs in KRAS(G12V) overexpressed cells, was found to exhibit a potent growth-inhibitory and proapoptotic effect both in vitro and in vivo. miR-4689 expression was significantly down-regulated in cancer tissues compared to normal mucosa, and it was particularly decreased in mutant KRAS CRC tissues. miR-4689 directly targets v-ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS) and v-akt murine thymoma viral oncogene homolog 1(AKT1), key components of two major branches in EGFR pathway, suggesting KRAS overdrives this signaling pathway through inhibition of miR-4689. Overall, this study provided additional evidence that mutant KRAS functions as a broad regulator of the EGFR signaling cascade by inhibiting miR-4689, which negatively regulates both RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT pathways. These activities indicated that miR-4689 may be a promising therapeutic agent in mutant KRAS CRC.
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Registered trials
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.