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.

Keywords: LncRNAs; MYB; MiRNAs; Noncoding RNAs; Tumorigenesis.

Fig. 1

The diagram shows the schematic structure of the gene and protein of A-MYB, B-MYB and c-MYB. A The domain structures of A-MYB, B-MYB, and c-MYB. The MYB protein is diagrammed, with N-terminal on the left and C-terminal on the right. The labels at the bottom of the diagram indicate conserved domains. The MYB gene is located on chromosome 6q23.3 and encodes a transcription factor with an N-terminal DNA binding domain (DBD), a central transactivation domain (TAD), and a negative regulatory domain (NRD). Oncogenic activity requires the FAETL domain, the TPTPF domain conserved in the other MYB proteins, and the EVES domain that is involved in intra-molecular interactions and negative regulation. B MYB transcriptional elongation regulation model, and the effect of the interaction between ncRNAs and MYB on the occurrence and development of tumor cells

Fig. 2

Schematic of the biogenesis of miRNA and the functional mechanism of miRNA. MiRNAs directly bind to the 3′UTR of MYB to regulate MYB expression. If miRNA and MYB are completely complementary, then the combination of these miRNAs causes the degradation of MYB

Fig. 3

LncRNAs and circRNAs promote the expression of MYB through multiple signaling pathways. Some lncRNAs and circRNAs act as molecular sponges and bind to miRNAs, thereby upregulating the level of miRNA target genes. MALAT1 modulates the expression of cell cycle genes by regulating pre-mRNA alternative splicing

Fig. 4

The interaction between miRNAs and MYB is involved in tumor cell proliferation, apoptosis, angiogenesis, metastasis, senescence and drug resistance. LncRNAs promote the expression of MYB through multiple signaling pathways. A Some lncRNAs act as molecular sponges and bind to miRNAs, thereby upregulating the level of miRNA target genes. B LncRNAAK023391 plays its role by activating signaling pathways. C MALAT1 promotes cell proliferation by regulating pre-mRNA alternative splicing