Regulation of Cancer Aggressive Features in Melanoma Cells by MicroRNAs

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs with regulatory roles, which are involved in a broad spectrum of physiological and pathological processes, including cancer. A common strategy for identification of miRNAs involved in cell transformation is to compare malignant cells to normal cells. Here we focus on identification of miRNAs that regulate the aggressive phenotype of melanoma cells. To avoid differences due to genetic background, a comparative high-throughput miRNA profiling was performed on two isogenic human melanoma cell lines that display major differences in their net proliferation, invasion and tube formation activities. This screening revealed two major cohorts of differentially expressed miRNAs. We speculated that miRNAs up-regulated in the more-aggressive cell line contribute oncogenic features, while the down-regulated miRNAs are tumor suppressive. This assumption was further tested experimentally on five candidate tumor suppressive miRNAs (miR-31, -34a, -184, -185 and -204) and on one candidate oncogenic miRNA (miR-17-5p), all of which have never been reported before in cutaneous melanoma. Remarkably, all candidate Suppressive-miRNAs inhibited net proliferation, invasion or tube formation, while miR-17-5p enhanced cell proliferation. miR-34a and miR-185 were further shown to inhibit the growth of melanoma xenografts when implanted in SCID-NOD mice. Finally, all six candidate miRNAs were detected in 15 different metastatic melanoma specimens, attesting for the physiological relevance of our findings. Collectively, these findings may prove instrumental for understanding mechanisms of disease and for development of novel therapeutic and staging technologies for melanoma.

MicroRNA-185 suppresses growth and invasion of colon cancer cells through inhibition of the hypoxia-inducible factor-2α pathway in vitro and in vivo

“…miR-185 was found to suppress glioma cell invasion, indicating that it may be a potential prognostic marker and therapeutic target (16). Previous studies have revealed that miR-185 impedes anchorage-independent growth, cell migration and invasion, in addition to suppressing tumor growth in vivo and increasing cisplatin sensitivity by promoting apoptosis, implicating it as a potent tumor suppressor (17)(18)(19). In the present study, overexpression of miR-185 repressed the growth and invasion of colon cancer cells in vitro and in vivo, which was consistent with the results of previous studies, indicating that miR-185 is a negative regulator of RhoA and Cdc42 and their cellular activities, and can inhibit the proliferation and invasion of CRC cells (20).…”

Novel Immunotherapy for Malignant Melanoma with a Monoclonal Antibody That Blocks CEACAM1 Homophilic Interactions

“…Net proliferation was determined by standardized XTT colorimetric assay (Biological Industries) as previously described (26).…”

MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer

“…miR-31 is reported to have tumor-suppressing functions, and its expression is decreased during tumorigenesis in several types of cancer, including breast, ovarian, prostate, bladder, hepatocellular, and gastric carcinoma and melanoma (9)(10)(11)(12)(13)(14)(15)(16). In contrast, a proproliferative function for miR-31 was reported in colorectal, head and neck squamous cell, small-cell lung, and esophageal squamous cell carcinoma (13,(17)(18)(19)(20).…”