Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, Anhui, China.
Department of Clinical Laboratory, Huaibei City People's Hospital, Huaibei, Anhui, China.
J Cell Physiol. 2020 Dec;235(12):9474-9486. doi: 10.1002/jcp.29755. Epub 2020 May 5.
Breast cancer is a malignant tumor with the highest incidence in women of the world. CXCR4 and Skp2 are highly expressed in breast cancer cells and CXCR4 was positively correlated with Skp2 by interference or overexpression. The microRNA array was used to detect the differentially expressed spectrum of micro RNAs in breast cancer cells the changes of miR-7-5p after CXCR4 inhibitor (NT21MP) treatment to block the CXCR4/SDF-1 pathway was founded. MiR-7-5p has been found to be correlated with Skp2 in various tumors in the literature, and Skp2 expression can be regulated by transfection with miR-7-5p mimics or inhibitors. The expression level of miR-7-5p was upregulated or downregulated after CXCR4 interference or overexpression. Combined with the correlation between CXCR4 and miR-7-5p in the chip results, CXCR4 may regulate Skp2 through miR-7-5p. Epithelial cells have the morphological characteristics of mesenchymal cells for some reason called epithelial-mesenchymal transformation (EMT). Transfection of miR-7-5p mimics into drug-resistant cells reduced Skp2 levels, decreased the expression of Vimentin, Snail, and slug, and increased the expression of E-cadherin. CXCR4 inhibitor (NT21MP) can reverse the EMT changes caused by miR-7-5p inhibitor. Similarly, in vivo results suggesting that CXCR4 inhibitors can reverse the EMT phenotype of drug-resistant breast cancer cells through the CXCR4/miR-7-5p/Skp2 pathway. In summary, the CXCR4/miR-7-5p/Skp2 signaling pathway plays an important role in the progression of breast cancer. This study provides a theoretical basis for the treatment of breast cancer by targeting the CXCR4 pathway.
乳腺癌是全球女性发病率最高的恶性肿瘤。CXCR4 和 Skp2 在乳腺癌细胞中高表达，CXCR4 通过干扰或过表达与 Skp2 呈正相关。利用 microRNA 芯片检测乳腺癌细胞中 microRNA 的差异表达谱，发现 CXCR4 抑制剂（NT21MP）阻断 CXCR4/SDF-1 通路后 miR-7-5p 的变化。文献中发现 miR-7-5p 与各种肿瘤中的 Skp2 相关，并且 Skp2 的表达可以通过转染 miR-7-5p 模拟物或抑制剂进行调节。CXCR4 干扰或过表达后，miR-7-5p 的表达水平上调或下调。结合芯片结果中 CXCR4 与 miR-7-5p 的相关性，CXCR4 可能通过 miR-7-5p 调节 Skp2。上皮细胞由于某种原因具有间充质细胞的形态特征，称为上皮-间充质转化（EMT）。转染 miR-7-5p 模拟物可降低耐药细胞中的 Skp2 水平，降低波形蛋白、Snail 和 slug 的表达，增加 E-钙黏蛋白的表达。CXCR4 抑制剂（NT21MP）可逆转 miR-7-5p 抑制剂引起的 EMT 变化。同样，体内结果表明，CXCR4 抑制剂可通过 CXCR4/miR-7-5p/Skp2 通路逆转耐药乳腺癌细胞的 EMT 表型。综上所述，CXCR4/miR-7-5p/Skp2 信号通路在乳腺癌的进展中起重要作用。本研究为靶向 CXCR4 通路治疗乳腺癌提供了理论依据。
