General information | Literature | Expression | Regulation | Mutation | Interaction |
Basic Information |
|
---|---|
Gene ID | 406940 |
Name | MIR148A |
Synonymous | MIRN148|MIRN148A|hsa-mir-148;microRNA 148a;MIR148A;microRNA 148a |
Definition | hsa-mir-148a|microRNA 148 |
Position | 7p15.2 |
Gene type | ncRNA |
Title |
Abstract |
A regulatory circuit of miR-148a/152 and DNMT1 in modulating cell transformation and tumor angiogenesis through IGF-IR and IRS1. | Dysregulation of microRNAs is a common feature in human cancers, including breast cancer (BC). Here we describe the epigenetic regulation of miR-148a and miR-152 and their impact on BC cells. Due to the hypermethylation of CpG island, the expression levels of both miR-148a and miR-152 (miR-148a/152) are decreased in BC tissues and cells. DNMT1, the DNA methyltransferase 1 for the maintenance methylation, is aberrantly up-regulated in BC and its overexpression is responsible for hypermethylation of miR-148a and miR-152 promoters. Intriguingly, we found that DNMT1 expression, which is one of the targets of miR-148a/152, is inversely correlated with the expression levels of miR-148a/152 in BC tissues. Those results lead us to propose a negative feedback regulatory loop between miR-148a/152 and DNMT1 in BC. More importantly, we demonstrate that IGF-IR and IRS1, often overexpressed in BC, are two novel targets of miR-148a/152. Overexpression of miR-148a or miR-152 significantly inhibits BC cell proliferation, colony formation, and tumor angiogenesis via targeting IGF-IR and IRS1 and suppressing their downstream AKT and MAPK/ERK signaling pathways. Our results suggest a novel miR-148a/152-DNMT1 regulatory circuit and reveal that miR-148a and miR-152 act as tumor suppressors by targeting IGF-IR and IRS1, and that restoration of miR-148a/152 expression may provide a strategy for therapeutic application to treat BC patients. |
MicroRNA-148a: a potential therapeutic target for cancer. | microRNA-148a (miR-148a) which suppresses tumor growth by directly decreasing DNMT1 expression has been demonstrated as an important role for cancer therapy. The mechanisms for miR-148a in cancer will become potential future researches. |