Interplay between cyclooxygenase‑2 and microRNAs in cancer (Review)

Abstract

Tumor‑associated inflammation and aberrantly expressed biomarkers have been demonstrated to play crucial roles in the cancer microenvironment. Cyclooxygenase‑2 (COX‑2), a prominent inflammatory factor, is highly expressed in tumor cells and contributes to tumor growth, recurrence and metastasis. Overexpression of COX‑2 may occur at both transcriptional and post‑transcriptional levels. Thus, an improved understanding of the regulatory mechanisms of COX‑2 can facilitate the development of novel antitumor therapies. MicroRNAs (miRNAs) are a group of small non‑coding RNAs that act as translation repressors of target mRNAs, and play vital roles in regulating cancer development and progression. The present review discusses the association between miRNAs and COX‑2 expression in different types of cancer. Understanding the regulatory role of miRNAs in COX‑2 post‑transcription can provide novel insight for suppressing COX‑2 expression via gene silencing mechanisms, which offer new perspectives and future directions for the development of novel COX‑2 selective inhibitors based on miRNAs.

Keywords: cyclooxygenase‑2; microRNAs; therapeutic target; cyclooxygenase‑2 inhibitors; cancer; inflammation.

Figure 1.

Interaction between COX-2 within the tumor microenvironment. Extracellular environment is exposed to inflammation, COX-2 is overexpressed in the cytoplasm of different types of cells, and converts arachidonic acid into prostaglandins and thromboxanes. PL, phospholipase; AA, arachidonic acid; COX, cyclooxygenase; NSAID, non-steroidal anti-inflammatory drugs; PG, prostaglandin; TXA, thromboxane.

Figure 2.

COX-2 acts as a pro-cancer enzyme. COX-2 is a stimulator for different types of cancer, which exerts multiple effects. COX-2, cyclooxygenase-2; MMP, matrix metalloproteinase; M2, macrophage type 2; EMT, epithelial-to-mesenchymal transition; CAF, cancer-associated fibroblast; CTL, cytotoxic T lymphocyte; IDO, indoleamine 2,3-dioxygenase; VEGF, vascular endothelial growth factor.