Department of General Surgery, Xinxiang Center Hospital, Xinxiang, Henan 453000, P.R. China.
Department of Oncology, People's Hospital of Xixia County, Nanyang, Henan 474550, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1707-1714. doi: 10.3892/mmr.2017.6816. Epub 2017 Jun 20.
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.
微小 RNA（miRs）是一类长度为 18-25 个核苷酸的非编码 RNA，作为人类癌症发生和发展的关键调节因子。先前已有研究表明 miR-503 与乳腺癌有关。然而，miR-503 调节乳腺癌细胞增殖和侵袭的潜在机制在很大程度上仍不清楚。在本研究中，逆转录-定量聚合酶链反应分析表明，与配对的相邻正常组织相比，乳腺癌组织中 miR-503 的表达显著降低。此外，与 T1 期相比，T2-T4 期乳腺癌 miR-503 的表达水平明显降低。胰岛素样生长因子 1 受体（IGF-1R）被进一步鉴定为 miR-503 的一个新靶标。miR-503 的过表达显著抑制 IGF-1R 的蛋白表达水平。此外，通过 MTT 和 Transwell 测定法分别评估，miR-503 过表达显著抑制了人乳腺癌 MCF-7 细胞的增殖和侵袭。然而，IGF-1R 表达的恢复显著改善了 miR-503 过表达对 MCF-7 细胞增殖和侵袭的抑制作用，表明 miR-503 通过直接靶向 IGF-1R 至少部分抑制乳腺癌细胞的增殖和侵袭。此外，与配对的相邻正常组织相比，乳腺癌组织中 IGF-1R 的 mRNA 和蛋白表达水平明显升高。此外，在乳腺癌中 IGF-1R mRNA 表达水平与 miR-503 表达水平呈负相关，表明 IGF-1R 的上调可能是由于乳腺癌中 miR-503 的下调。总之，本研究扩展了对 miR-503 在乳腺癌中调节机制的理解，并提示 miR-503/IGF-1R 轴可能是乳腺癌的潜在治疗靶点。
