Abstract
MicroRNAs (miRNAs) regulate gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report that expression of miR-205 is significantly suppressed in melanoma specimens when compared with nevi and is correlated inversely with melanoma progression. miRNA target databases predicted E2F1 and E2F5 as putative targets. The expression levels of E2F1 and E2F5 were correlated inversely with that of miR-205 in melanoma cell lines. miR-205 significantly suppressed the luciferase activity of reporter plasmids containing the 3'-UTR sequences complementary to either E2F1 or E2F5. Overexpression of miR-205 in melanoma cells reduced E2F1 and E2F5 protein levels. The proliferative capacity of melanoma cells was suppressed by miR-205 and mediated by E2F-regulated AKT phosphorylation. miR-205 overexpression resulted in induction of apoptosis, as evidenced by increased cleaved caspase-3, poly-(ADP-ribose) polymerase, and cytochrome c release. Stable overexpression of miR-205 suppressed melanoma cell proliferation, colony formation, and tumor cell growth in vivo and induced a senescence phenotype accompanied by elevated expression of p16INK4A and other markers for senescence. E2F1 overexpression in miR-205-expressing cells partially reversed the effects on melanoma cell growth and senescence. These results demonstrate a novel role for miR-205 as a tumor suppressor in melanoma.
Highlights
MicroRNAs2 are a class of short noncoding RNAs that regulate gene expression by complementary base pairing with the 3Ј-UTR of target mRNAs and causing their degradation [1] or by directly mediating mRNA degradation [2]
Deregulation of miRNA expression has been identified in a number of cancers [5, 6], and accumulating data indicate that some miRNAs can function as tumor suppressors or oncogenes and as such are important in cancer development
MiR-205 Is Down-regulated in Melanoma, and Its Expression Is Inversely Correlated with That of E2F1 and E2F5—To determine the expression pattern of miRNAs in melanoma, we performed a miRNA microarray on a small number of nevi, primary, and metastatic tumor samples (n ϭ 5 per group) using the Agilent platform
Summary
MicroRNAs (miRNAs) are a class of short noncoding RNAs that regulate gene expression by complementary base pairing with the 3Ј-UTR of target mRNAs and causing their degradation [1] or by directly mediating mRNA degradation [2]. It is difficult to identify accurately individual miRNA-target interactions, computational predictions of miRNA target genes indicate that as many as one-third of all human protein-encoding genes may be regulated by miRNAs [10]. Due to their tremendous regulatory potential and tissueand disease-specific expression patterns, there is increasing evidence that miRNA expression profiles could be indicative of disease risk or burden. E2F5, another E2F family member, is an oncogenic cell cycle regulator demonstrated to be amplified or overexpressed in various tumors [17, 18]. We examine the consequences of miR-205 overexpression and identify E2F1 and E2F5 as downstream targets of miR-205 action in melanoma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
