Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature cells derived from bone marrow that play critical immunosuppressive functions in the tumor microenvironment (TME), promoting cancer progression. According to base length, Non-coding RNAs (ncRNAs) are mainly divided into: microRNAs (miRNAs), lncRNAs, snRNAs and CircRNAs. Both miRNA and lncRNA are transcribed by RNA polymerase II, and they play an important role in gene expression under both physiological and pathological conditions. The increasing data have shown that MiRNAs/LncRNAs regulate MDSCs within TME, becoming one of potential breakthrough points at the investigation and treatment of cancer. Therefore, we summarize how miRNAs/lncRNAs mediate the differentiation, expansion and immunosuppressive function of tumor MDSCs in TME. We will then focus on the regulatory mechanisms of exosomal MicroRNAs/LncRNAs on tumor MDSCs. Finally, we will discuss how the interaction of miRNAs/lncRNAs modulates tumor MDSCs.
Highlights
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population derived from bone marrow progenitor cells and immature myeloid cells [1]
Tumor-secreted factors Granulocyte-macrophage colony stimulating factor (GM-CSF)/ IL-6 upregulate high expression levels of miR-21a/21b/181b through STAT3/CEBPb pathway, further diminishing the expression of WD repeat-containing protein 5 (Wdr5), absent small or homeotic-like (ASH2L) and mixed lineage leukemia 1 (MLL1), which are involved in the expansion and differentiation of Granulocytic MDSCs (G-MDSCs)
When Mir-155 was silenced, the expression of target lncRNA was significantly increased. These results indicated that miRNA could regulate the expression of lncRNA [89]. lncRNAs can act as one Competing endogenous RNA (ceRNA) to sequester miRNAs, regulating the abundance and activity of miRNAs, resulting in the de-repression of genes targeted by corresponding miRNAs in cancer progression [34, 90]
Summary
MDSCs are a heterogeneous population derived from bone marrow progenitor cells and immature myeloid cells [1]. MiRNAs are non-coding single-stranded small RNAs of approximately 22-24 nucleotides in length and are highly conserved evolutionarily, and are widely found in eukaryotic cells They play vital regulatory roles in cells, especially in mRNA post-transcriptional regulation, and reduce mRNA expression levels by binding to the 3’UTR of mRNA and binding to the 5 ‘-UTR of mRNA to upregulate its transcription [10–12]. MiRNAs are involved in regulating both a wide range of physiological activities such as cell cycle, differentiation, proliferation, maturation and immune response and pathological processes, such as inflammation and cancer [13]. LncRNAs themselves can interact with other ncRNAs, such as miRNAs [30] Both miRNA and lncRNA are transcribed by RNA polymerase II, and they play important roles in gene expression under both physiological and pathological conditions, as transcriptional and post-transcriptional regulators [28]. The abnormal expression of miRNAs/lncRNAs in MDSCs and their regulatory mechanism on MDSCs have become potential breakthrough points
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