MicroRNAs, TGF-β signaling, and the inflammatory microenvironment in cancer

Abstract

Inflammatory cells and mediators form a major part of the tumor microenvironment and play important roles in the regulation of cancer initiation, tumor cell proliferation, and metastasis. MicroRNAs (miRNAs) play important roles in several physiological and pathological processes, including the regulation of the inflammatory microenvironment in cancer. Transforming growth factor-β (TGF-β) is an inflammation-related cytokine that functions in both tumor suppression and promotion; however, its underlying molecular mechanisms remain unclear. Recent evidence indicates an association between miRNAs and TGF-β signaling, providing new insight into the nature of the inflammatory microenvironment in cancer. The present review is an overview of the interaction between miRNAs and inflammatory cytokines, with emphasis on the cross talk between TGF-β signaling and miRNAs and their influence on cancer cell behavior. The emerging roles of miRNAs in cancer-related inflammation and the potential to target miRNA signaling pathways for cancer therapy are also discussed.

Keywords: Cancer; Inflammatory microenvironment; MicroRNA; TGF-β signaling.

Fig. 1

Overview of the interaction of cytokines in the inflammatory tumor microenvironment. Tumor-associated inflammation develops simultaneously with tumor development. The tumor microenvironment is a complex scaffold of various cells and extracellular matrix. Different cells contribute by producing cytokines and respond to stimuli secreted by other cells. This creates a favorable microenvironment for tumor growth and progression. The inflammatory response plays a central role in angiogenesis, tumor proliferation, local immunosuppression, and metastasis

Fig. 2

The TGF-β signaling pathway and related miRNAs. Ligand binding to the TGF-β receptor (TβR)-mediated heterotetramer formation. This signal is relayed through the nucleus via restricted Smad (R-Smad). Activated R-Smads complex with common Smads (Co-Smad, such as Smad-4) translocate to the nucleus and alter miRNA transcription. In addition, TGF-β signaling alteration of miRNA transcription may depend on non-Smad molecules, such as ERKs, JNK/p38, RhoA, and PI3K/Akt. The mechanisms of TGF-β signaling-mediated miRNA expression are either transcriptional or post-transcriptional