From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that play an important role in regulating gene expression at a posttranscriptional level. As one of the first discovered oncogenic miRNAs, microRNA-21 (miR-21) has been highlighted for its critical role in cancers, such as glioblastoma, pancreatic adenocarcinoma, non-small cell lung cancer, and many others. MiR-21 targets many vital components in a wide range of cancers and acts on various cellular processes ranging from cancer stemness to cell death. Expression of miR-21 is elevated within cancer tissues and circulating miR-21 is readily detectable in biofluids, making it valuable as a cancer biomarker with significant potential for use in diagnosis and prognosis. Advances in RNA-based therapeutics have revealed additional avenues by which miR-21 can be utilized as a promising target in cancer. The purpose of this review is to outline the roles of miR-21 as a key modulator in various cancers and its potential as a therapeutic target.

MicroRNA-nanoparticles against cancer: Opportunities and challenges for personalized medicine

“…MiR-21, strongly upregulated in aggressive gastric cancer, triggers cell proliferation, invasion, and migration by remodeling the extracellular matrix and downmodulating key apoptotic genes like the tumor suppressor RECK. 24 MiR-192 and miR-215 can promote cell proliferation and migration, via APC inhibition and the Wnt signaling activation, thus inducing gastric cancer progression. 25 MiR-1275 regulates gastric cancer cell lipid signaling by reverting the oncogenic effects mediated by fatty acid amide hydrolase, through the downregulation of arachidonoyl ethanolamide (AEA)/lysophosphatidic acid (LPA) signaling and activation of the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis, thereby affecting gastric cancer progression.…”

The significance of the crosstalk between ubiquitination or deubiquitination and ncRNAs in non-small cell lung cancer

“…MiR-21 is one of cancer research’s first identified “miRNA enhancers” ( 32 ). All cells in the human body can produce extracellular vesicles (EVs), which are membranous vesicles released into the extracellular matrix.…”

“…MiR-21 was significantly higher in sputum and plasma samples from patients with NSCLC than healthy donors. Thus, in addition to promoting growth and invasion phenotypes, miR-21 is a non-invasive biomarker for NSCLC diagnosis ( 32 , 34 ). Recent studies have focused on the combined effects of let-7 and miR-21.…”

Role of exosomal ncRNAs released by M2 macrophages in tumor progression of gastrointestinal cancers

“… 83 MiR-21 is considered as an oncogenic effect in different tumors, and its overexpression can promote solid tumor development. 84 Thus, miR-21 inhibition may reduce fibrosis and suppress populations of immunosuppressive cells simultaneously, thereby slowing premalignant progression and shrinking the tumors. 85 Overall, M2-TAMs-Exos-ncRNAs are essential for tumor growth, development, and in drug resistance.…”