32P Immunoregulatory loop between let-7a and CCAT1 lncRNA coordinated by c-Myc underlies the PD-1/PD-L1 immunoresistance in triple negative breast cancer patients

Selem, N.; Nafae, Heba; Youness, R.A.

doi:10.1016/j.annonc.2021.08.2028

Cited by 7 publications

(5 citation statements)

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“…Moreover, this led in a significant increase in primary immune cells cytotoxicity upon co-culturing with transfected Huh7 cells. Our results were consistent with recent reports highlighting the immunomodulatory role of CCAT-1 [81] , H19 [32] and MALAT-1 [49] in several solid malignancies.…”

Section: Discussionsupporting

confidence: 94%

A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma

Assal,

Elemam,

Mekky

et al. 2024

Translational Oncology

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Section: Discussionsupporting

confidence: 94%

A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma

Assal,

Elemam,

Mekky

et al. 2024

Translational Oncology

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“…Therefore, a positive feedback loop among CCAT-1 and c-Myc boosts cancer cell aggressiveness by increasing the expression of each gene. Myc gene amplification is common in many solid tumor types, while chromosomal translocation is common in B-cell/T-cell leukemias and lymphomas; Myc is activated in about 70% of HNSCC via amplification or pathway activation (128). The detailed mechanisms of Myc activation by Based on mechanisms that contribute to concomitant activation, the master transcription factors NF-kB, STAT3, FOXO, AKT and Myc bind the promoter of LIN28 and PD-L1 and upregulate their expressions.…”

Section: Stat3/nf-kb/c-myc and Pd-l1mentioning

confidence: 99%

Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy

Xiao

et al. 2023

Front. Oncol.

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The development of techniques and immunotherapies are widely applied in cancer treatment such as checkpoint inhibitors, adoptive cell therapy, and cancer vaccines apart from radiation therapy, surgery, and chemotherapy give enduring anti-tumor effects. Minority people utilize single-agent immunotherapy, and most people adopt multiple-agent immunotherapy. The difficulties are resolved by including the biomarkers to choose the non-responders’ and responders’ potentials. The possibility of the potential complications and side effects are examined to improve cancer therapy effects. The Head and Neck Squamous Cell Carcinoma (HNSCC) is analyzed with the help of programmed cell death ligand 1 (PD-L1) and Insulin-like growth factor (IGF). But how IGF and PD-L1 upregulation depends on IL-6, EGFR, and LIN28/Let7-related mechanisms are poorly understood. Briefly, IL-6 stimulates gene expressions of IGF-1/2, and IL-6 cross-activates IGF-1R signaling, NF-κB, and STAT3. NF-κB, up-regulating PD-L1 expressions. IL-6/JAK1 primes PD-L1 for STT3-mediated PD-L1 glycosylation, stabilizes PD-L1 and trafficks it to the cell surface. Moreover, ΔNp63 is predominantly overexpressed over TAp63 in HNSCC, elevates circulating IGF-1 levels by repressing IGFBP3, and activates insulin receptor substrate 1 (IRS1).TP63 and SOX2 form a complex with CCAT1 to promote EGFR expression. EGFR activation through EGF binding extends STAT3 activation, and EGFR and its downstream signaling prolong PD-L1 mRNA half-life. PLC-γ1 binding to a cytoplasmic motif of elevated PD-L1 improves EGF-induced activation of inositol 1,4,5-tri-phosphate (IP3), and diacylglycerol (DAG) subsequently elevates RAC1-GTP. RAC1-GTP was convincingly demonstrated to induce the autocrine production and action of IL-6/IL-6R, forming a feedback loop for IGF and PD-L1 upregulation. Furthermore, the LIN28-Let7 axis mediates the NF-κB-IL-6-STAT3 amplification loop, activated LIN28-Let7 axis up-regulates RAS, AKT, IL-6, IGF-1/2, IGF-1R, Myc, and PD-L1, plays pivotal roles in IGF-1R activation and Myc, NF-κB, STAT3 concomitant activation. Therefore, based on a detailed mechanisms review, our article firstly reveals that IL-6, EGFR, and LIN28/Let7-related mechanisms mediate PD-L1 and IGF upregulation in HNSCC, which comprehensively influences immunity, inflammation, metabolism, and metastasis in the tumor microenvironment, and might be fundamental for overcoming therapy resistance.

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“…ncRNAs regulating the PD-1/PD-L1 axis are able to change the sensitivity of cells toward pembrolizumab. For instance, miRNA-34a, 138, 200c, 424, and 570, let-7a, and lncRNAs CCAT1 and GATA3-AS1 can regulate tumor growth and proliferation through PD-L1 modulation, and thus response to immunotherapy [98][99][100]. In a clinical trial (KEYNOTE-086), Loi et al, using RNA-seq-based data, confirmed that inflammatory state signatures obtained by measuring the tissue-resident memory are asso-ciated with the response to pembrolizumab in TNBC patients [101].…”

Section: Discussionmentioning

confidence: 99%

Blood Circulating Non-Coding RNAs for the Clinical Management of Triple-Negative Breast Cancer

Powrózek

Otieno

2022

Cancers

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Triple negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, and is related to unfavorable prognosis and limited treatment strategies. Currently, there is a lack of reliable biomarkers allowing for the clinical management of TNBC. This is probably caused by a complex molecular background, leading to the development and establishment of a unique tumor phenotype. Recent studies have reported non-coding RNAs (ncRNAs) not only as the most promising class of molecular agents with a high applicability to manage human cancers, including TNBC, but also as robust and non-invasive biomarkers that are able to be monitored in blood circulation, with the application of liquid biopsy. There is a lack of papers discussing the role of blood-circulating ncRNAs as diagnostic, predictive, and prognostic biomarkers for TNBC. In this paper, we summarized the available literature reports on the utility of blood-circulating ncRNAs for TNBC management. Additionally, we supplemented this review by bioinformatics analysis, for better understanding of the role of ncRNAs’ machinery in the development of a unique TNBC phenotype.

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32P Immunoregulatory loop between let-7a and CCAT1 lncRNA coordinated by c-Myc underlies the PD-1/PD-L1 immunoresistance in triple negative breast cancer patients

Cited by 7 publications

References 0 publications

A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma

A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma

Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy

Blood Circulating Non-Coding RNAs for the Clinical Management of Triple-Negative Breast Cancer

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