MicroRNA-18b May Act as Tumor Suppressor in Melanoma

Researchers have identified a microRNA that has potential to be a diagnostic and prognostic biomarker for patients with melanoma.

Preclinical analyses have indicated that microRNA-18b (miR-18b) may have a role as a tumor suppressor, has the potential to be a biomarker for melanoma, and its overexpression may be a novel therapeutic strategy for the treatment of melanoma, according to the results of a study published in the Journal of the National Cancer Institute.

“Little was known about the functional role of miR-18b in human cancer,” said Mohammed Kashani-Sabet, MD, from the Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco.

“In one prior study, miR-18b levels were increased in gastric cancer, suggesting a possible oncogenic role,” he said. “However, this study clearly showed that miR-18b levels are suppressed in melanoma-by virtue of hypermethylation-demonstrating a tumor suppressor function.”

Kashani-Sabet and colleagues analyzed miR-18b expression in 48 nevi samples and 92 melanoma samples using immunoblotting to determine the expression of proteins regulated by the microRNA.

The analysis indicated that expression of miR-18b was reduced or silenced in both melanoma specimens and in melanoma cell lines when compared with nevi and normal melanocytes. This result indicates that levels of miR-18b could potentially be used to differentiate benign moles from melanomas and to identify those melanomas with a higher risk of spreading, Kashani-Sabet said.

The researchers subsequently identified MDM2 as a target of miR-18b action. Recent research has shown that MDM2 may play a role in cancer progression, and that targeting this oncogene results in apoptosis and inhibits proliferation.

Conversely, the researchers analyses indicated that overexpression of miR-18b led to the downregulation of MDM2 and the activation of p53.

According to Kashani-Sabet, this result is significant because it represents a novel mechanism by which p53 can be suppressed in melanoma.

“The p53 gene is an important tumor suppressor gene that is lost in many cancers by virtue of point mutations in the gene,” Kashani-Sabet said. “Melanomas are somewhat unique among solid tumors in that p53 mutations occur rather infrequently.”

There is also considerable interest in reactivation of p53 as a therapeutic strategy for human cancer, according to Kashani-Sabet. This study suggests overexpression of miR-18b as a novel way to reactivate p53 and suppress the growth of human cancers.