BACKGROUND & AIMS:
: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.
背景与目标:
: microrna (miRs) 是一类长度为18-25个核苷酸的非编码rna,是人类癌症发生和发展的关键调节剂。以前,mir-503与乳腺癌有关。然而,mir-503在调节乳腺癌细胞增殖和侵袭中的潜在机制在很大程度上仍然未知。在本研究中,逆转录定量聚合酶链反应分析表明,与匹配的邻近正常组织相比,乳腺癌组织中mir-503的表达显着降低。此外,与T1期相比,T2-T4期乳腺癌的mir-503表达水平显著降低。胰岛素样生长因子1受体 (igf ‑ 1R) 被进一步鉴定为mir-503的新靶标。Mir-503的过表达显著抑制igf ‑ 1R的蛋白表达水平。此外,它抑制人乳腺癌mcf ‑ 7细胞的增殖和侵袭,分别通过MTT和tranwell分析评估。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至少部分通过直接靶向igf ‑ 1R来抑制乳腺癌细胞增殖和侵袭。此外,与匹配的邻近正常组织相比,乳腺癌组织中igf ‑ 1R的mRNA和蛋白表达水平显着增加。此外,igf ‑ 1R mRNA表达水平与乳腺肿瘤中的503表达水平呈反向相关,这表明igf ‑ 1R的上调可能是由于乳腺癌中mir-503的下调所致。总之,本研究扩大了对乳腺癌中mir-503调控机制的理解,并暗示mir-503/igf ‑ 1R轴是乳腺癌的潜在治疗靶标。