The Interplay among miRNAs, Major Cytokines, and Cancer-Related Inflammation

Abstract

Inflammation is closely related with the progression of cancer and is an indispensable component that orchestrates the tumor microenvironment. Studies suggest that different mediator and cellular effectors, including cytokines (interleukins, tumor necrosis factor-α [TNF-α], transforming growth factor-β [TGF-β], and granulocyte macrophage colony-stimulating factor [GM-CSF]), chemokines, as well as some transcription factors (nuclear factor κB [NF-κB], signal transducer and activator of transcription 3 [STAT3], hypoxia-inducible factor-1α [HIF1α]), play a crucial role during cancer-related inflammation (CRI). MicroRNAs (miRNAs) are the key components of cellular physiology. They play notable roles during posttranscriptional gene regulation and, thus, might have a potential role in controlling the inflammatory cascade during cancer progression. Taking into consideration the role identified for miRNAs in relation to inflammatory cytokines, we have tried to review their participation in neoplastic progression. Additionally, the involvement of miRNAs with some important transcription factors (NF-κB, STAT3, HIF1α) and proteins (cyclooxygenase-2 [COX-2], inducible nitric oxide synthase [iNOS]) closely associated with inflammation during cancer has also been discussed. A clear insight into the responsibility of miRNAs in cytokine signaling and inflammation related to CRI could project them as new therapeutic molecules, which could lead to improved treatment of CRI in the near future.

Keywords: cancer; cytokines; inflammation; miRNA; tumor microenvironment.

Graphical abstract

Figure 1

Pathway Depicting the Process of the Cancer-Related Inflammation and Mediators Involved during This Cascade

Figure 2

Summary of the Inflammatory Microenvironment in Cancer Development The tumor microenvironment plays an important role in the process of cancer development. In this microenvironment, pro-inflammatory cytokine (secreted by the inflammatory cell) modulates NF-κB, STAT3, and HIF1α, which activates iNOS and COX-2. iNOS and COX-2 proteins help in the cancer initiation and progression process. The inflammatory cells present in the inflammatory microenvironment also activates the production of matrix metallopeptidases (MMPs), monocyte chemoattractant protein (MCP), as well as cytokines, which results in cancer progression, invasion, and metastasis.

Figure 3

Schematic Diagram Depicting miRNA-Controlled Cytokine Cascades in Cancer-Related Inflammation (TNF-α, IL-1, IL-6, IL-17, IL-23, TGF-β, GM-CSF)

Figure 4

Schematic Diagram Shows miRNAs That Control Other Significant Proteins (Other Than the Cytokines) Associated with CRI (NF-κB, STAT3, HIF1α, iNOS, COX-2, PPARγ)