ArticleInternational journal of molecular sciences2022
HNMT Upregulation Induces Cancer Stem Cell Formation and Confers Protection against Oxidative Stress through Interaction with HER2 in Non-Small-Cell Lung Cancer.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- HNMT promotes the motility-associated structures of breast cancer cells through the PI3K/Akt signaling pathway to promote tumor progression.Histology and histopathology · 2026Article
- Oxidative Stress Defense Module in Lung Cancers: Molecular Pathways and Therapeutic Approaches.Antioxidants (Basel, Switzerland) · 2025Review
- HNMT Promotes the Occurrence and Progression of Nasopharyngeal Carcinoma by Inhibiting the IFN/TXNIP/p53 Axis.Current medical science · 2025Article
- Article
- Multi-omics profiling reveals PLEKHA6 as a modulator of β-catenin signaling and therapeutic vulnerability in lung adenocarcinoma.American journal of cancer research · 2025Article
- Chemical Profiling, Antioxidant, and Antiproliferative Activities of AlgerianCurrent topics in medicinal chemistry · 2025Article
- Prognostic Prediction and Immune Microenvironment Characterization in Uveal Melanoma: A Novel Mitochondrial Metabolism-Related Gene Signature.ACS omega · 2024Article
- MiR-223-3p in Cancer Development and Cancer Drug Resistance: Same Coin, Different Faces.International journal of molecular sciences · 2024Review
- Value of prognostic nutritional index and controlling nutritional status score for advanced non-small cell lung cancer patients receiving PD-1 inhibitors.American journal of cancer research · 2024Article
- Penetrating Exploration of Prognostic Correlations of the FKBP Gene Family with Lung Adenocarcinoma.Journal of personalized medicine · 2022Article
- Novel Potential Therapeutic Targets of PTPN Families for Lung Cancer.Journal of personalized medicine · 2022Article
- Article
- Comprehensive analysis of prognostic significance of cadherin (CDH) gene family in breast cancer.Aging · 2022Article
- Redox-Regulation in Cancer Stem Cells.Biomedicines · 2022Review
- Prediction of prognosis and immunotherapy response of amino acid metabolism genes in acute myeloid leukemia.Frontiers in nutrition · 2022Article
- Current treatments for non-small cell lung cancer.Frontiers in oncology · 2022Review
- Investigation of M2 macrophage-related gene affecting patients prognosis and drug sensitivity in non-small cell lung cancer: Evidence from bioinformatic and experiments.Frontiers in oncology · 2022Article
- The Risk Model Based on the Three Oxidative Stress-Related Genes Evaluates the Prognosis of LAC Patients.Oxidative medicine and cellular longevity · 2022Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundThe treatment of non-small-cell lung cancer (NSCLC) involves platinum-based chemotherapy. It is typically accompanied by chemoresistance resulting from antioxidant properties conferred by cancer stem cells (CSCs). Human epidermal growth factor receptor 2 (HER2) enhances CSCs and antioxidant properties in cancers, including NSCLC.
methodsHere, we elucidated the role of histamine N-methyltransferase (HNMT), a histamine metabolism enzyme significantly upregulated in NSCLC and coexpressed with HER2. HNMT expression in lung cancer tissues was determined using quantitative reverse transcription PCR (RT-qPCR). A publicly available dataset was used to determine HNMT's potential as an NSCLC target molecule. Immunohistochemistry and coimmunoprecipitation were used to determine HNMT-HER2 correlations and interactions, respectively. HNMT shRNA and overexpression plasmids were used to explore HNMT functions in vitro and in vivo. We also examined miRNAs that may target HNMT and investigated HNMT/HER2's role on NSCLC cells' antioxidant properties. Finally, how HNMT loss affects NSCLC cells' sensitivity to cisplatin was investigated.
resultsHNMT was significantly upregulated in human NSCLC tissues, conferred a worse prognosis, and was coexpressed with HER2. HNMT depletion and overexpression respectively decreased and increased cell proliferation, colony formation, tumorsphere formation, and CSCs marker expression. Coimmunoprecipitation analysis indicated that HNMT directly interacts with HER2. TARGETSCAN analysis revealed that HNMT is a miR-223 and miR-3065-5p target. TBHp treatment increased HER2 expression, whereas shHNMT disrupted the Nuclear factor erythroid 2-related factor 2 (Nrf2)/ hemeoxygenase-1 (HO-1)/HER2 axis and increased reactive oxygen species accumulation in NSCLC cells. Finally, shHNMT sensitized H441 cells to cisplatin treatment in vitro and in vivo.
conclusionsTherefore, HNMT upregulation in NSCLC cells may upregulate HER2 expression, increasing tumorigenicity and chemoresistance through CSCs maintenance and antioxidant properties. This newly discovered regulatory axis may aid in retarding NSCLC progression and chemoresistance.
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