MicroRNAs (miRNAs) are small non-coding RNA molecules, approximately 22 nucleotides in length that regulate gene translation through silencing or degradation of target mRNAs. They are involved in multiple biological processes, including differentiation and proliferation, metabolism, hemostasis, apoptosis or inflammation, and in pathophysiology of many diseases. Numerous studies have suggested circulating miRNAs as promising diagnostic and prognostic biomarkers of many diseases.
MiR-222 and miR-221 are two highly homologous microRNAs located in tandem on the X chromosome in human, mouse and rat and are highly conserved in vertebrates. Moreover, they have the same seed sequence and it was indicated that miR-222 was co-transcribed in a cluster with miR-221.
Overexpression of the cluster miR-221/222 has been recently described in several types of human tumors and miR-221/222 are considered to act as oncogenes or tumor suppressors, depending on tumor system.
Cell cycle regulator p27Kip1 was identified as a target of miR-221/miR-222. It was shown that in pancreatic cells, p27Kip1 and miR-221/222 expression levels inversely correlated and that miR221/222 overexpression had important consequences on the proliferation rate and the cell cycle phase distribution. These results were then confirmed in glioblastomas, in thyroid papillary carcinomas, in breast cancer, hepatocellular carcinoma, and lung cancer.
MiR-222-3p was conﬁrmed to exhibit higher expression level in oral squamous cell carcinoma (OSCC). Up-regulation of miR-222-3p in OSCC was found in the tissue but not in plasma when compared to normal tissues.
Abnormal expression of miR-222-3p has been also reported in breast cancer and osteosarcoma (OS). It has been demonstrated that miR-222-3p was upregulated in OS tissues and OS cell lines. Moreover, inhibition of miR-222-3p can suppress OS cell proliferation, colony formation, and invasion in vitro.
In addition, several studies indicate that miR-221/222 have a prominent role in acquisition of anti-estrogen resistance and that miR221/222 overexpression is linked to altered response to cancer therapy, either to hormone-based or to conventional chemotherapy.
- References to miR-222-3p