Antitumor Activity of miR-1280 in Melanoma by Regulation of Src

Abstract

MicroRNAs (miRNAs) play a key role in cancer progression by coordinately repressing target genes involved in cell proliferation, migration, and invasion. miRNAs regulate gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report that expression of miR-1280 is significantly suppressed in human melanoma specimens when compared with nevi, and in human melanoma cell lines when compared with cultured normal human melanocytes. The proto-oncogene Src was identified as a target of miR-1280 action. Levels of Src expression were significantly higher in melanoma samples and cell lines than in nevi and normal melanocytes. miR-1280 overexpression significantly suppressed the luciferase activity of reporter plasmids containing the full-length 3' untranslated region of Src. miR-1280-mediated suppression of Src led to substantial decreases in melanoma cell proliferation, cell cycle progression, invasion, as well as induced melanoma cell apoptosis. The effects of miR-1280 overexpression on melanoma cell proliferation and growth were reversed by Src overexpression. Intratumoral delivery of miR-1280 significantly suppressed melanoma cell growth in vivo. Our results demonstrate a novel role for miR-1280 as a tumor suppressor in melanoma, identify the Src signaling pathway as a target of miR-1280 action, and suggest a potential therapeutic role for miR-1280 in melanoma.

tRF/miR-1280 Suppresses Stem Cell–like Cells and Metastasis in Colorectal Cancer

“…Many recent studies have reported the expression and role of "miR-1280" in various cancer types (12)(13)(14)(15)(16)(17). In melanoma cells, "miR-1280" displays antitumor activity by regulating the proto-oncogene Src (12).…”

“…Many recent studies have reported the expression and role of "miR-1280" in various cancer types (12)(13)(14)(15)(16)(17). In melanoma cells, "miR-1280" displays antitumor activity by regulating the proto-oncogene Src (12). "miR-1280" can inhibit invasion and metastasis by targeting Rock1 in bladder cancer cells, and the high-miR-1280 bladder cancer group had significantly higher overall survival probability compared with the low-miR-1280 group (13).…”

Tissue tRNA‐Derived Fragments (tRFs) as Potential Candidates Correlate with Invasiveness in Colorectal Carcinomas

“…tRF/ miR-1280 overexpression leads to suppress proliferation and invasive ability to melanoma cell. all of the above-mentioned data can be suggested that it represents a promising molecular target for anticancer therapy (33). The opposite results in the early stage of primary Non-small Cell Lung Cancer (NSCLC) patients reported that increasing rate of tRF/miR-1280 can inhibit proliferation signaling pathways (34) .…”

Small molecules targeting microRNA for cancer therapy: Promises and obstacles

“…85 For example, Sun et al reported the role of miR-1280 in suppressing melanoma by regulating Src, which acts as proto-oncogenes by mediating tumor proliferation and invasion. 86 Intratumoral injection of miR-1280 complexed with the siPORT transfection reagent significantly suppressed melanoma progression in vivo . Tiwari et al proved that oral squamous cell carcinoma cells with overexpressed miR-125a showed reduced proliferation and invasion since estrogen-related receptor α was significantly downregulated.…”