MicroRNA 221 (miR-221) (miR-221)

MicroRNA 221 (miR-221) is a small non-coding RNA that functions as a significant oncogenic driver (oncomiR) across a wide range of human cancers, including hepatocellular carcinoma, breast cancer, and glioblastoma [1, 2, 4]. It exerts its biological effects primarily by post-transcriptionally repressing key tumor suppressor genes such as CDKN1B (p27), CDKN1C (p57), and PTEN, which leads to accelerated cell cycle progression, increased proliferation, and resistance to apoptosis [1, 5, 8]. When packaged into exosomes, miR-221 serves as a critical mediator of intercellular communication, promoting angiogenesis and metastasis within the tumor microenvironment [6, 10, 12]. Beyond its role in oncology, exosomal miR-221 is involved in cardiovascular pathologies, such as myocardial infarction and fibrosis, where its levels in circulation serve as stable diagnostic and prognostic biomarkers [13, 14, 17]. Therapeutic strategies targeting miR-221 utilize antisense oligonucleotides, most notably Locked Nucleic Acid (LNA) inhibitors like LNA-i-miR-221, which are designed to silence the miRNA and restore the expression of its target suppressors [3, 7, 18]. Early clinical evaluations of these inhibitors have demonstrated potential in managing refractory solid tumors by modulating the miR-221-regulated signaling axes [7].

Other names

MIR221hsa-miR-221hsa-miR-221-3pExosomal microRNA 221MicroRNA 221/222 cluster

Antisense inhibition of microRNA-221 using locked nucleic acids (LNAs) or antagomirs to prevent the silencing of target tumor suppressor mRNAs (e.g., p27, PTEN), thereby restoring normal cell cycle control and promoting apoptosis in malignant cells [3, 7, 18].