MicroRNA-221 and MicroRNA-222 in Common Human Cancers

Expression, Function, and Triggering of Tumor Progression as a Key Modulator

Sima Amini, MSc; Atefe Abak, MSc; Ebrahim Sakhinia, PhD; Alireza Abhari, PhD

Disclosures

Lab Med. 2019;50(4):333-347. 

In This Article

Effective Role of MiR-221/-222 in Triggering Malignant Tumors

MiR-221/-222 are overexpressed in different types of malignant neoplasms, including non–small-cell lung carcinoma (NSCLC), colorectal carcinoma, breast cancer, hepatocellular carcinoma (HCC), glioblastoma, bladder cancer, prostate cancer, melanoma, and ovarian cancer.[31,47–50] In a report,[12] Stinson et al reported a greater amount of miR-221 and miR-222 in basal-like breast cancer (BLBC), compared with the luminal type. They identified that these miRNAs were abundant in basal B, which is more aggressive than basal A. Also, through this research, the researchers found that these miRNAs were more abundant in triple-negative breast cancer (TNBC) than estrogen receptor (ER)–/progesterone receptor (PR)–positive ones.

Also, Garofalo et al,[31] reported that miR-222 is widely overexpressed in HCC and NSCLC, compared with less-invasive and healthy lung and liver cells. In addition, 4 NSCLC cell lines were recently assessed[51] in terms of miR-221 and miR-222, which illustrates the high expression of miR-221 and miR-222 in tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–resistant and TRAIL-semiresistant cell lines, compared with TRAIL-sensitive cells.

Another study[52] provided evidence that miR-222 exosomal expression frequently reflected its abundance in melanoma-origination cells, precisely paralleled through suppression of its target genes, such as cyclin-dependent kinase inhibitor 1B (p27Kip1), and induction of the phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathway. Therefore, expression of miR-222 exosomal expression can confirm its functional implication and its ability to increase tumor malignancy in melanoma in humans. Another research report[19] shows the reverse relationship among the expression of miR-221/-222 and the cell-cycle inhibitor p27Kip1 which, through ectopic overexpression of these miRNAs directly, can lead to downregulation of p27 in lymph-node carcinoma of the prostate (LNCaP) cells.

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