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.

译文

:MicroRNA(miRs)是一类长度为18-25个核苷酸的非编码RNA,在人类癌症的发生和发展中起着关键的调节作用。以前,miR‑503与乳腺癌有关。但是,miR-503调控乳腺癌细胞增殖和侵袭的潜在机制仍然未知。在本研究中,逆转录定量聚合酶链反应分析表明,与癌旁相匹配的正常组织相比,miR‑503的表达在乳腺癌组织中显着降低。此外,与T1期相比,T2‑T4期乳腺癌中miR‑503表达水平显着降低。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的过表达显着抑制了IGF‑1R的蛋白质表达水平。此外,分别通过MTT和Transwell分析评估,它抑制了人乳腺癌MCF-7细胞的增殖和侵袭。但是,IGF-1R表达的恢复显着改善了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抑制了乳腺癌细胞的增殖和侵袭。此外,与匹配的邻近正常组织相比,在乳腺癌组织中,IGF-1R的mRNA和蛋白表达水平得到了显着提高。此外,乳腺肿瘤中IGF-1R mRNA表达水平与miR-503表达水平呈负相关,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miR‑503在乳腺癌中调控机制的理解,并暗示miR‑503 / IGF‑1R轴可作为乳腺癌的潜在治疗靶标。

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