Splicing deregulation, microRNA and notch aberrations: fighting the three-headed dog to overcome drug resistance in malignant mesothelioma

Anobile, Dario P.; Montenovo, Giulia; Pecoraro, Camilla; Frańczak, Marika; Iddouch, Widad Ait; Peters, Godefridus J.; Riganti, Chiara; Giovannetti, Elisa

doi:10.1080/17512433.2022.2074835

Cited by 8 publications

(6 citation statements)

References 167 publications

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“…Moreover, KEGG analysis on RNA-seq data showed the dominant pathway is STAT3/NOTCH1 signaling pathway. Recent studies have revealed that the aberrant activation of STAT3/Notch1 signaling play a critical role in the interaction between cancer stemness and therapy resistance [23,24], targeting STAT3/Notch1 signaling may inhibit the development of cancer stemness and reverse platinum-based chemoresistance [25,26].…”

Section: Discussionmentioning

confidence: 99%

L-Theanine inhibits cancer stem cell-mediated chemoresistance in lung cancer by regulating STAT3/NOTCH1-BMAL1 signaling

Jin,

Su,

You

et al. 2023

Preprint

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Cancer stem cells play crucial roles in the development of cancer chemoresistance. L-Theanine, a nonproteinogenic amino acid derived from green tea, is gaining more and more attentions in reversing cancer drug resistance. However, its roles in development of lung cancer chemoresistance is still unknown. To investigate the effects of L-Theanine on chemoresistance and explore its underlying mechanism in lung cancer, we performed a panel of experiments in vitro combined with RNA-seq analysis and demonstrated L-Theanine improved the chemoresistance to cisplatin (cis-diamminedichloroplatinum; DDP) and inhibited stemness of DDP-resistant lung cancer cells but not non-resistant lung cancer cells and STAT3/NOTCH1 signaling was a potential dominant process involved in L-Theanine improving chemoresistance in DDP-resistant lung cancer. Mechanistically, L-Theanine impedes DDP-resistant lung cancer cells migration and activation via regulating the expression of STAT3/NOTCH1/BMAL1 signaling-induced stemness markers, reducing the migration and proliferation of DDP-resistant lung cancer cells as well as inhibiting drug resistance-related genes expression in DDP-resistant lung cancer cells. In addition, combination of L-Theanine and Stat3 blockade improved synergistically the chemoresistance in DDP-resistant lung cancer. In summary, L-Theanine improved chemoresistance in chemoresistant lung cancer through regulating STAT3/NOTCH1/BMAL1 signaling, reducing stemness and finally inhibiting the migration of DDP-resistant lung cancer cells. The finding might provide the research evidence for therapeutic options of reversing chemoresistance in lung cancer.

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Section: Discussionmentioning

confidence: 99%

L-Theanine inhibits cancer stem cell-mediated chemoresistance in lung cancer by regulating STAT3/NOTCH1-BMAL1 signaling

Jin,

Su,

You

et al. 2023

Preprint

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“…In recent years, epigenetic modification has been widely studied. Existing evidence shows that epigenetic modification exists in various molecular biological processes, and it has a significant role in the occurrence and development of cancer 27 – 31 . As the more critical one, m 6 A RNA modification has also been shown to have an important direct relationship with cancers 32 – 36 .…”

Section: Discussionmentioning

confidence: 99%

Gene signature of m6A RNA regulators in diagnosis, prognosis, treatment, and immune microenvironment for cervical cancer

Wang

Ding

Wang

et al. 2022

Sci Rep

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Continuing studies imply that m6A RNA modification is involved in the development of cervical cancer (CC), but lack strong support on recurrence and diagnosis prediction. In this research, a comprehensive analysis of 33 m6A regulators was performed to fulfill them. Here, we performed diagnostic and prognosis models and identified key regulators, respectively. Then the CC patients were separated into two clusters in accordance with 33 regulators, and participants in the cluster 1 had a worse prognosis. Subsequently, the m6AScore was calculated to quantify the m6A modification pattern based on regulators and we found that patients in cluster 1 had higher m6AScore. Afterwards, immune microenvironment, cell infiltration, escape analyses and tumor burden mutation analyses were executed, and results showed that m6AScore was correlated with them, but to a limited extent. Interestingly, HLAs and immune checkpoint expression, and immunophenoscore in patients with high-m6AScores were significantly lower than those in the low-m6AScore group. These suggested the m6AScores might be used to predict the feasibility of immunotherapy in patients. Results provided a distinctive perspective on m6A modification and theoretical basis for CC diagnosis, prognosis, clinical treatment strategies, and potential mechanism exploration.

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“…The Notch signaling pathway also enriches CSCs and regulates the EMT program in multiple cancers, including breast and lung cancer, pancreatic ductal adenocarcinoma, and malignant mesothelioma. [151][152][153][154][155] A previous finding showed a change in EMT status in lung adenocarcinoma upon treatment with gefitinib. 156 Subsequent studies further confirmed that the EMT process resulted from the activation of Notch-1 signaling pathway and led to gefitinib-acquired resistance.…”

Section: Epigenetic Mechanismsmentioning

confidence: 95%

Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies

Pang

Yang

et al. 2023

Sig Transduct Target Ther

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Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to a complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed to circumvent tumor cell plasticity, including epigenetic modifications, regulation of transcription factors, activation or suppression of key signaling pathways, as well as modification of the tumor environment. Epithelial-to-mesenchymal transition, tumor cell and cancer stem cell formation also serve as roads towards tumor cell plasticity. Corresponding treatment strategies have recently been developed that either target plasticity-related mechanisms or employ combination treatments. In this review, we delineate the formation of tumor cell plasticity and its manipulation of tumor evasion from targeted therapy. We discuss the non-genetic mechanisms of targeted drug-induced tumor cell plasticity in various types of tumors and provide insights into the contribution of tumor cell plasticity to acquired drug resistance. New therapeutic strategies such as inhibition or reversal of tumor cell plasticity are also presented. We also discuss the multitude of clinical trials that are ongoing worldwide with the intention of improving clinical outcomes. These advances provide a direction for developing novel therapeutic strategies and combination therapy regimens that target tumor cell plasticity.

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Splicing deregulation, microRNA and notch aberrations: fighting the three-headed dog to overcome drug resistance in malignant mesothelioma

Cited by 8 publications

References 167 publications

L-Theanine inhibits cancer stem cell-mediated chemoresistance in lung cancer by regulating STAT3/NOTCH1-BMAL1 signaling

L-Theanine inhibits cancer stem cell-mediated chemoresistance in lung cancer by regulating STAT3/NOTCH1-BMAL1 signaling

Gene signature of m6A RNA regulators in diagnosis, prognosis, treatment, and immune microenvironment for cervical cancer

Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies

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