MiR-323a regulates ErbB3/EGFR and blocks gefitinib resistance acquisition in colorectal cancer

Zhang, Yuanzhou; Liang, Shunshun; Xiao, Bowen; Hu, Jun; Pang, Yu; Liu, Yuling; Yang, Juan; Ao, Junpin; Wei, Lin; Luo, Xiaoying

doi:10.1038/s41419-022-04709-9

Cited by 8 publications

(3 citation statements)

References 59 publications

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“…EGFR is closely associated with CRC recurrence and deterioration. Studies have demonstrated that miR-323a-3p can promote the apoptosis of CRC cells by directly targeting EGFR signaling[ 28 ]. Acquired resistance to 5-fluorouracil is a clinical challenge for CRC treatment.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and molecular docking-based analyses to predict the potential mechanism of Huangqin decoction in treating colorectal cancer

Li¹,

Tang²,

Yan³

et al. 2023

World J Clin Cases

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BACKGROUND To analyze the potential action mechanism of Huangqin decoction (HQD) in colorectal cancer (CRC) treatment on the basis of network pharmacology and molecular docking. AIM To investigate the molecular mechanisms of HQD for CRC treatment by using network pharmacology and molecular docking. METHODS All HQD active ingredients were searched using the Systematic Pharmacology and Traditional Chinese Medicine Systems Pharmacology databases and the Bioinformatics Analysis Tool for Molecular Mechanisms in traditional Chinese medicine. Then, the targets of the active ingredients were screened. The abbreviations of protein targets were obtained from the UniProt database. A “drug–compound–target” network was constructed to screen for some main active ingredients. Some targets related to the therapeutic effect of CRC were obtained from the GeneCards, DisGeNET, Therapeutic Target Database, and Online Mendelian Inheritance in Man databases. The intersection of targets of Chinese herbs and CRC was taken. A Venn diagram was drawn to construct the intersection target interactions network by referring to the STRING database. Topological analysis of the protein interaction network was performed using Cytoscape 3.7.2 software to screen the core HQD targets for CRC. The core targets were imported into the DAVID 6.8 analysis website for gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses and visualization. Finally, molecular docking was performed using AutoDockTool and PyMOL for validation. RESULTS In total, 280 potential drug-active ingredients were present in HQD, including 1474 targets of the drug-active ingredients. The main active ingredients identified were betulin, tetrahydropalmatine, and quercetin. In total, 10249 CRC-related targets and 1014 drug-disease intersecting targets were identified, including 28 core targets of action such as Jun proto-oncogene, AP-1 transcription factor subunit, signal transducer and activator of transcription 3, tumor protein p53, vascular endothelial growth factor, and AKT serine/threonine kinase 1. The gene ontology enrichment functional analysis yielded 503 enrichment results, including 406 biological processes that were mainly related to the positive regulation of both gene expression and transcription and cellular response to hypoxia, etc. In total, 38 cellular components were primarily related to polymer complexes, transcription factor complexes, and platelet alpha granule lumen. Then, 59 molecular functions were closely related to the binding of enzymes, homologous proteins, and transcription factors. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded 139 enrichment results, involving epidermal growth factor receptor tyrosine kinase inhibitor resistance and HIF-1 and mitogen-activated protein kinase signaling pathways. CONCLUSION HQD can play a role in CRC treatment thro...

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Section: Discussionmentioning

confidence: 99%

Network pharmacology and molecular docking-based analyses to predict the potential mechanism of Huangqin decoction in treating colorectal cancer

Li¹,

Tang²,

Yan³

et al. 2023

World J Clin Cases

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“…An elevation in EGFR/HER3 dimerization was detected in BC patients, which led to PI3K/AKT signal transduction and cetuximab/panitumumab resistance [ 33 ] . EGFR/HER3 was activated in gefitinib-resistant CRC cells, miR-323a-3p reversed ErbB3/EGFR signaling activation and blocked acquired gefitinib resistance [ 34 ] . MET amplification drove HER3-dependent activation of PI3K and subsequently caused EGFR TKI gefitinib and erlotinib resistance in NSCLC [ 35 ] .…”

Section: The Mechanism Of Her3 In Drug Resistancementioning

confidence: 99%

HER3-targeted therapy: the mechanism of drug resistance and the development of anticancer drugs

Zeng,

Wang,

Zhang

et al. 2024

Cancer Drug Resist

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Human epidermal growth factor receptor 3 (HER3), which is part of the HER family, is aberrantly expressed in various human cancers. Since HER3 only has weak tyrosine kinase activity, when HER3 ligand neuregulin 1 (NRG1) or neuregulin 2 (NRG2) appears, activated HER3 contributes to cancer development and drug resistance by forming heterodimers with other receptors, mainly including epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Inhibition of HER3 and its downstream signaling, including PI3K/AKT, MEK/MAPK, JAK/STAT, and Src kinase, is believed to be necessary to conquer drug resistance and improve treatment efficiency. Until now, despite multiple anti-HER3 antibodies undergoing preclinical and clinical studies, none of the HER3-targeted therapies are licensed for utilization in clinical cancer treatment because of their safety and efficacy. Therefore, the development of HER3-targeted drugs possessing safety, tolerability, and sensitivity is crucial for clinical cancer treatment. This review summarizes the progress of the mechanism of HER3 in drug resistance, the HER3-targeted therapies that are conducted in preclinical and clinical trials, and some emerging molecules that could be used as future designed drugs for HER3, aiming to provide insights for future research and development of anticancer drugs targeting HER3.

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“…The overexpression of miR-217 in COC1 cells facilitated CDDP-induced apoptosis and enhanced CDDP sensitivity by inhibiting the activation of the Wnt/b-catenin signaling pathway (146). In addition, multiple miRNAs, such as miR-323a-3p, miR-6727-5p, and miRNA-223-3p, have also been found to contribute to the development of cancer drug resistance by regulating apoptotic pathways via targeting other drug resistance-related signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-kB) signaling pathways (147)(148)(149). Collectively, these findings indicate that targeting the apoptotic pathways is a common regulation mechanism for miRNAs in cancer drug resistance.…”

Section: Mirnas and Cancer Drug Resistance Mirnas Affect Drug-induced...mentioning

confidence: 99%

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

Zhou

Jia

et al. 2022

Front. Oncol.

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Cancer is one of the most frequently diagnosed malignant diseases worldwide, posing a serious, long-term threat to patients’ health and life. Systemic chemotherapy remains the first-line therapeutic approach for recurrent or metastatic cancer patients after surgery, with the potential to effectively extend patient survival. However, the development of drug resistance seriously limits the clinical efficiency of chemotherapy and ultimately results in treatment failure and patient death. A large number of studies have shown that non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RNAs, and circular RNAs, are widely involved in the regulation of cancer drug resistance. Their dysregulation contributes to the development of cancer drug resistance by modulating the expression of specific target genes involved in cellular apoptosis, autophagy, drug efflux, epithelial-to-mesenchymal transition (EMT), and cancer stem cells (CSCs). Moreover, some ncRNAs also possess great potential as efficient, specific biomarkers in diagnosis and prognosis as well as therapeutic targets in cancer patients. In this review, we summarize the recent findings on the emerging role and underlying mechanisms of ncRNAs involved in cancer drug resistance and focus on their clinical applications as biomarkers and therapeutic targets in cancer treatment. This information will be of great benefit to early diagnosis and prognostic assessments of cancer as well as the development of ncRNA-based therapeutic strategies for cancer patients.

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MiR-323a regulates ErbB3/EGFR and blocks gefitinib resistance acquisition in colorectal cancer

Cited by 8 publications

References 59 publications

Network pharmacology and molecular docking-based analyses to predict the potential mechanism of Huangqin decoction in treating colorectal cancer

Network pharmacology and molecular docking-based analyses to predict the potential mechanism of Huangqin decoction in treating colorectal cancer

HER3-targeted therapy: the mechanism of drug resistance and the development of anticancer drugs

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

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