MN1, FOXP1 and hsa-miR-181a-5p as prognostic markers in acute myeloid leukemia patients treated with intensive induction chemotherapy and autologous stem cell transplantation

Seipel, Katja; Messerli, Christian; Wiedemann, Gertrud; Bacher, Ulrike; Pabst, Thomas

doi:10.1016/j.leukres.2020.106296

Cited by 24 publications

(16 citation statements)

References 27 publications

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“…A case in point is hsa-miR-181a-5p belonging to miR-181 family can target several m6A regulators in BRCA, LIHC, LUSC, and UCEC ( Figure 2C). The hsa-miR-181a-5p has been reported to be associated with acute myeloid leukemia, papillary thyroid cancer, endometrial carcinoma and so on (52)(53)(54). Some m6A regulators, such as HNRNPC, HNRNPA2B1, and FTO, can also be targeted by several miRNAs ( Figure 2D).…”

Section: Identification Of Mirnas Targeting M6a Regulators In Pan-cancermentioning

confidence: 97%

Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers

et al. 2021

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BackgroundN6-methyladenosine (m6A), the most abundant chemical modification on eukaryotic messenger RNA (mRNA), is modulated by three class of regulators namely “writers,” “erasers,” and “readers.” Increasing studies have shown that aberrant expression of m6A regulators plays broad roles in tumorigenesis and progression. However, it is largely unknown regarding the expression regulation for RNA m6A regulators in human cancers.ResultsHere we characterized the expression profiles of RNA m6A regulators in 13 cancer types with The Cancer Genome Atlas (TCGA) data. We showed that METTL14, FTO, and ALKBH5 were down-regulated in most cancers, whereas YTHDF1 and IGF2BP3 were up-regulated in 12 cancer types except for thyroid carcinoma (THCA). Survival analysis further revealed that low expression of several m6A regulators displayed longer overall survival times. Then, we analyzed microRNA (miRNA)-regulated and DNA methylation-regulated expression changes of m6A regulators in pan-cancer. In total, we identified 158 miRNAs and 58 DNA methylation probes (DMPs) involved in expression regulation for RNA m6A regulators. Furthermore, we assessed the survival significance of those regulatory pairs. Among them, 10 miRNAs and 7 DMPs may promote cancer initiation and progression; conversely, 3 miRNA/mRNA pairs in kidney renal clear cell carcinoma (KIRC) may exert tumor-suppressor function. These findings are indicative of their potential prognostic values. Finally, we validated two of those miRNA/mRNA pairs (hsa-miR-1307-3p/METTL14 and hsa-miR-204-5p/IGF2BP3) that could serve a critical role for potential clinical application in KIRC patients.ConclusionsOur findings highlighted the importance of upstream regulation (miRNA and DNA methylation) governing m6A regulators’ expression in pan-cancer. As a result, we identified several informative regulatory pairs for prognostic stratification. Thus, our study provides new insights into molecular mechanisms of m6A modification in human cancers.

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Section: Identification Of Mirnas Targeting M6a Regulators In Pan-cancermentioning

confidence: 97%

Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers

et al. 2021

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“…In addition to p53 and RREB1, miR-145 is regulated by other transcription factors, including CCAAT/enhancer-binding protein beta (C/EBPβ), beta-catenin/T cell factor 4 (TCF4), and forkhead transcription factors FOXO1 and FOXO3 in human cancers [36,37]. The transcriptional co-factor meningioma 1 (MN1) gene is highly expressed, and its upregulation is inversely correlated with miR-20a and miR-181b transcripts in acute myeloid leukemia (AML) patients [38]. The c-Myc oncogenic transcription factor (MYC) transactivates expression of the miR-17~92 cluster (also known as oncomiR-1), and MYC-activated miR-17~92 promotes cancer progression by controlling expressions of E2F1, connective tissue growth factor (CTGF), thrombospondin 1 (THBS1), and phosphatase and tensin homolog (PTEN) in multiple cancers [39][40][41][42][43]77].…”

Section: Modulation Of Mirna Expression By Transcription Factors In Cancermentioning

confidence: 99%

Regulatory Mechanism of MicroRNA Expression in Cancer

Syeda

Langden

Munkhzul

et al. 2020

IJMS

709

415

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Altered gene expression is the primary molecular mechanism responsible for the pathological processes of human diseases, including cancer. MicroRNAs (miRNAs) are virtually involved at the post-transcriptional level and bind to 3′ UTR of their target messenger RNA (mRNA) to suppress expression. Dysfunction of miRNAs disturbs expression of oncogenic or tumor-suppressive target genes, which is implicated in cancer pathogenesis. As such, a large number of miRNAs have been found to be downregulated or upregulated in human cancers and to function as oncomiRs or oncosuppressor miRs. Notably, the molecular mechanism underlying the dysregulation of miRNA expression in cancer has been recently uncovered. The genetic deletion or amplification and epigenetic methylation of miRNA genomic loci and the transcription factor-mediated regulation of primary miRNA often alter the landscape of miRNA expression in cancer. Dysregulation of the multiple processing steps in mature miRNA biogenesis can also cause alterations in miRNA expression in cancer. Detailed knowledge of the regulatory mechanism of miRNAs in cancer is essential for understanding its physiological role and the implications of cancer-associated dysfunction and dysregulation. In this review, we elucidate how miRNA expression is deregulated in cancer, paying particular attention to the cancer-associated transcriptional and post-transcriptional factors that execute miRNA programs.

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“…In hepatocellular carcinoma: miR-181 was reported to significantly turn on the MAPK/JNK pathway, the regulator of cell proliferation, and by limiting it, would suppress the pathway [ 36 ]. Hsa-miR-181a-5p, a tumour suppressor is considered as a prognostic marker in Acute Myeloid Leukemia patients treated with intensive induction chemotherapy and autologous stem cell transplant [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Hsa-miR-181a-5p, hsa-miR-182-5p, and hsa-miR-26a-5p as potential biomarkers for BCR-ABL1 among adult chronic myeloid leukemia treated with tyrosine kinase inhibitors at the molecular response

et al. 2022

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Background Tyrosine kinase inhibitors (TKIs) as first-line therapy for Chronic Myeloid Leukemia (CML) show a high success rate. However, a low number of patients with long-term treatment-free remission (TFR) were observed. Molecular relapse after imatinib discontinuation occurred at 50% at 24 months, with 80% occurrence within the first 6 months. One of the reasons for relapse is untimely TKIs discontinuation caused by large errors from estimates at very low-level or undetectable disease, thus warranting new biomarkers for CML. Methods Next Generation Sequencing (NGS) was used to identify microRNAs (miRNAs) at the molecular response in CML adult patients receiving TKIs treatment. A total of 86 samples were collected, 30 from CML patients responsive and 28 from non-responsive to imatinib therapy, and 28 from blood donors. NGS was conducted whereby 18 miRNAs were selected and validated by real-time RT-qPCR in triplicate. Results Hsa-miR-181a-5p was expressed significantly (p-value< 0.05) with 2.14 and 2.33-fold down-regulation in both patient groups, respectively meanwhile hsa-miR-182-5p and hsa-miR-26a-5p were significant only in the non-responsive group with 2.08 and 2.39 fold up-regulation. The down-regulation was consistent with decreased amounts of BCR-ABL1 in patients taking TKIs regardless of molecular responses. The up-regulation was consistent with the substantial presence of BCR-ABL1 in CML patients treated with TKIs at the molecular response. Conclusions Therefore, these miRNAs have potential as new therapeutic biomarkers for BCR-ABL1 status in adult CML patients treated with TKIs at molecular responses. These could improve current approaches and require further analysis to look for targets of these miRNAs in CML.

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MN1, FOXP1 and hsa-miR-181a-5p as prognostic markers in acute myeloid leukemia patients treated with intensive induction chemotherapy and autologous stem cell transplantation

Cited by 24 publications

References 27 publications

Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers

Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers

Regulatory Mechanism of MicroRNA Expression in Cancer

Hsa-miR-181a-5p, hsa-miR-182-5p, and hsa-miR-26a-5p as potential biomarkers for BCR-ABL1 among adult chronic myeloid leukemia treated with tyrosine kinase inhibitors at the molecular response

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