Intricate crosstalk between MYB and noncoding RNAs in cancer

Abstract

MYB is often overexpressed in malignant tumors and plays a carcinogenic role in the initiation and development of cancer. Deletion of the MYB regulatory C-terminal domain may be a driving mutation leading to tumorigenesis, therefore, different tumor mechanisms produce similar MYB proteins. As MYB is a transcription factor, priority has been given to identifying the genes that it regulates. All previous attention has been focused on protein-coding genes. However, an increasing number of studies have suggested that MYB can affect the complexity of cancer progression by regulating tumor-associated noncoding RNAs (ncRNAs), such as microRNAs, long-non-coding RNAs and circular RNAs. ncRNAs can regulate the expression of numerous downstream genes at the transcription, RNA processing and translation levels, thereby having various biological functions. Additionally, ncRNAs play important roles in regulating MYB expression. This review focuses on the intricate crosstalk between oncogenic MYB and ncRNAs, which play a pivotal role in tumorigenesis, including proliferation, apoptosis, angiogenesis, metastasis, senescence and drug resistance. In addition, we discuss therapeutic strategies for crosstalk between MYB and ncRNAs to prevent the occurrence and development of cancer.

Biphasic transcriptional and posttranscriptional regulation of MYB by androgen signaling mediates its growth control in prostate cancer

“…Posttranscriptional regulation of MYB via miRNA-mediated mechanisms has been demonstrated in multiple cancer cell types and during the cellular differentiation ( 32 , 33 , 34 ). Also, several miRNAs have been identified to exhibit aberrant expression in PCa and play a role in pathobiology and therapy resistance ( 35 , 36 ).…”

role of miRNA -150 between different BCR-ABL p210 transcript levels and between different levels of imatinib optimal response in CML patients

“…These findings show that miRNA signatures could be used as biomarkers in CML research, allowing for CML staging and predicting patient response to TKI therapy [20]. MYB mRNA stability and translation efficiency are both affected by miR-150, MYB has been shown to be a top predicted target of miR-150, furthermore, miR-150 can target MYB in chronic myeloid leukemia (CML) and limit the production of a number of oncogenes, preventing CML cells from proliferating [19]. MYB is a confirmed target of miR-150.…”

“…When comparison differential expression of microRNAs in CML patients who responded to TKI therapy ("responders") versus those who did not ("non responders"), as well as between normal control bone marrow cells and CML patients' leukemic cells The goal is to identify microRNAs as predictive biomarkers of TKI sensitivity as well as to aid in the investigation of potential microRNA mediated TKI resistance mechanisms for therapeutic use [19]. MiRNA levels in the blood were shown to alter considerably in newly diagnosed CML patients before and throughout the first two weeks of Imatinib treatment, suggesting the possibility of identifying easily detectable biomarkers to track TKI response.…”

Emerging role of MYB transcription factors in cancer drug resistance

“…In addition, the combination of MYB antisense phosphorothioate ODNs with cisplatin was active against LoVo/Dx CRC tumors in vitro and in vivo [ 146 ] . Antisense drugs targeting non-coding RNAs and miRNA-based drugs are also promising strategies to suppress MYB in cancers [ 147 ] . In terms of immune therapy, the treatment with the MYB-targeting TetMYB DNA vaccine showed prophylactic effects in adenomatous polyposis mouse models and overcame anti-PD-1 resistance in MYB-expressing CT26 and MC38 CRC models by increased CD8 + T-cell activation [ 148 , 149 ] .…”