Abstract
Patients with triple-negative breast cancers (TNBCs) typically have a poor prognosis. TNBCs are characterized by their resistance to apoptosis, aggressive cellular proliferation, migration and invasion, and currently lack molecular markers and effective targeted therapy. Recently, miR-221/miR-222 have been shown to regulate ERα expression and ERα-mediated signaling in luminal breast cancer cells, and also to promote EMT in TNBCs. In this study, we characterized the role of miR-221 in a panel of TNBCs as compared to other breast cancer types. miR-221 knockdown not only blocked cell cycle progression, induced cell apoptosis, and inhibited cell proliferation in-vitro but it also inhibited in-vivo tumor growth by targeting p27kip1. Furthermore, miR-221 knockdown inhibited cell migration and invasion by altering E-cadherin expression, and its regulatory transcription factors Snail and Slug in human TNBC cell lines. Therefore, miR-221 functions as an oncogene and is essential in regulating tumorigenesis in TNBCs both in vitro as well as in vivo.
Highlights
MicroRNAs are non-coding, single-stranded,22 nucleotides long small RNAs that act as agents of the RNA interference pathway and negatively regulate the translation by either cleaving or degrading their targeted transcripts [1]
Clustered with miR-221, the expression level of miR-222 is only up-regulated mildly (1–1.5 fold) in Hs-578-T and BT-20, but down regulated in MDA-MB-468 and the other non-triple-negative breast cancers (TNBCs) lines tested (Figure 1B). These results indicate that miR-221/ miR-222 are both down-regulated in non-TNBC cells, miR-221 is over-expressed in the TNBC cell lines in comparison to normal breast tissue
Since highly activated cell proliferation is one of the major characteristics of TNBCs, we investigated whether miR-221 targets p27kip1in this particular breast cancer subtype
Summary
MicroRNAs (miRNAs) are non-coding, single-stranded ,22 nucleotides long small RNAs that act as agents of the RNA interference pathway and negatively regulate the translation by either cleaving or degrading their targeted transcripts [1]. Because miRNAs usually bind to their targets with incomplete complementarity, a single miRNA can potentially regulate the translation of multiple target genes involved in various cellular processes [2,3]. MiRNAs have been implicated in the regulation of a variety of biological functions, including cellular proliferation, differentiation, and apoptosis [4,5]. Growing evidence indicates that miRNAs can function as tumor suppressors or oncogenes [4], and miRNA expression profiling analyses have revealed characteristic miRNA signatures in a variety of human cancers [6,7]. Since miRNAs are believed to be pivotal players in tumor development, investigations of differential expression of miRNAs and their corresponding targets might prove to be instrumental for the diagnosis and treatment of various cancers
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