MicroRNA-503 inhibits the proliferation and invasion of breast cancer cells via targeting insulin-like growth factor 1 receptor.

Abstract

MicroRNAs (miRs), a class of non-coding RNAs that are 18–25 nucleotides in length, serve as key regulators in the development and progression of human cancers. Previously, miR-503 has been implicated in breast cancer. However, the underlying mechanism of miR-503 in regulating the proliferation and invasion of breast cancer cells remains largely unknown. In the present study, reverse transcription-quantitative polymerase chain reaction analysis indicated that the expression of miR-503 was significantly reduced in breast cancer tissues compared with their matched adjacent normal tissues. Furthermore, miR-503 expression levels were markedly reduced in T2-T4 stage breast cancer, compared with T1 stage. Insulin-like growth factor 1 receptor (IGF-1R) was further identified as a novel target of miR-503. Overexpression of miR-503 significantly suppressed the protein expression levels of IGF-1R. Furthermore, it inhibited the proliferation and invasion of human breast cancer MCF-7 cells, as assessed by MTT and Transwell assays, respectively. However, restoration of IGF-1R expression markedly ameliorated the suppressive effects of miR-503 overexpression on MCF-7 cell proliferation and invasion, indicating that miR-503 inhibits breast cancer cell proliferation and invasion at least partially via directly targeting IGF-1R. Furthermore, the mRNA and protein expression levels of IGF-1R were demonstrated to be significantly increased in breast cancer tissues compared with their matched adjacent normal tissues. In addition, IGF-1R mRNA expression levels were reversely correlated with miR-503 expression levels in breast tumors, suggesting that the upregulation of IGF-1R may be due to downregulation of miR-503 in breast cancer. In conclusion, the present study expanded the understanding of the regulatory mechanism of miR-503 in breast cancer, and implicates the miR-503/IGF-1R axis as a potential therapeutic target for breast cancer.