ArticleJournal of experimental & clinical cancer research : CR2021
M6A associated TSUC7 inhibition contributed to Erlotinib resistance in lung adenocarcinoma through a notch signaling activation dependent way.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 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
34 citing papers in PubMed, 90 citations in OpenAlex.
- Multiomics profiling and experiments in preclinical models revealed RAD51-IN-1 as a synergistic potentiator of anlotinib sensitivity.Science advances · 2026Trial
- Inhibiting METTL3 synergizes with Notch blockade to treat ESCC by targeting cancer stemness via m6A-JAG2.Journal of gastroenterology · 2026Article
- The lncRNA-m6A axis in cancer: a bidirectional regulatory network in tumor progression and therapeutic resistance.Journal of translational medicine · 2026Review
- Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.Experimental hematology & oncology · 2026Review
- The role of m6A modification in non-small cell lung cancer: functional insights and impact on therapy resistance.Cancer cell international · 2025Review
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- Reciprocal regulation between m6 A modifications and non-coding RNAs: emerging roles in cancer therapeutic resistance.Discover oncology · 2025Review
- The changing treatment landscape of EGFR-mutant non-small-cell lung cancer.Nature reviews. Clinical oncology · 2025Review
- The epitranscriptome meets non-coding RNA: m6A-mediated regulation in oncogenesis and therapy.Frontiers in cell and developmental biology · 2025Review
- SLC50A1 inhibits the doxorubicin sensitivity in hepatocellular carcinoma cells through regulating the tumor glycolysis.Cell death discovery · 2024Article
- Epitranscriptomic RNA mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Decoding the epitranscriptome: a new frontier for cancer therapy and drug resistance.Cell communication and signaling : CCS · 2024Review
- Writers, readers, and erasers RNA modifications and drug resistance in cancer.Molecular cancer · 2024Review
- Refining the optimal CAF cluster marker for predicting TME-dependent survival expectancy and treatment benefits in NSCLC patients.Scientific reports · 2024Article
- Overview of the interplay between m6A methylation modification and non-coding RNA and their impact on tumor cells.Translational cancer research · 2024Review
- Association between methyltransferase-like 3 and non-small cell lung cancer: pathogenesis, therapeutic resistance, and clinical applications.Translational lung cancer research · 2024Review
- The role of m6A methylation in targeted therapy resistance in lung cancer.American journal of cancer research · 2024Review
- Comprehensive landscape and future perspective of long noncoding RNAs in non-small cell lung cancer: it takes a village.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Correction: M6A associated TSUC7 inhibition contributed to Erlotinib resistance in lung adenocarcinoma through a notch signaling activation dependent way.Journal of experimental & clinical cancer research : CR · 2023Article
- The critical roles of m6A RNA methylation in lung cancer: from mechanism to prognosis and therapy.British journal of cancer · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects.
methodsMultiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections.
resultsWe explored the specific gene features of candidates in association with resistance, and found that m6A controlled the stemness of EMT features through METTL3 and YTHDF2. The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 suppressed TUSC7, both of which contributed to the resistant features. Functionally, the sponge type of TUSC7 regulation of miR-146a inhibited Notch signaling functions, and affected the cancer progression and stem cells' renewal in Erlotinib resistant PC9 cells (PC9ER) and Erlotinib resistant HCC827 cells (HCC827ER) cells. The Notch signaling functions manipulated the cMYC and DICER inner cytoplasm, and the absence of either cMYC or DICER1 lead to TUSC7 and miR-146a decreasing respectively, formed the closed circle to maintain the balance.
conclusionPC9ER and HCC827ER cells harbored much more stem-like cells, and the resistance could be reversed by Notch signaling inactivation. The intrinsic miR-146 and TUSC7 levels are monitored by m6A effectors, the alternation of either miR-146 or TUSC7 expression could lead to the circling loop to sustain the new homeostasis. Further in clinics, the combined delivery of TKIs and Notch specific inhibitory non-coding RNAs will pave the way for yielding the susceptibility to targeted therapy in lung cancer.
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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.