抑制CD36与Nogo-B表达抑制三阴性乳腺癌细胞增殖与迁移

Inhibition of CD36 and Nogo-B expression inhibited the proliferation and migration of triple negative breast cancer cells

摘要:

分化聚类36（cluster of differentiation 36，CD36）是一种位于细胞表面的膜蛋白受体，可以结合并转运脂肪酸。内质网膜蛋白4B （Nogo-B）在肝脏中调控脂肪酸代谢而影响肝癌的发展。目前并不清楚CD36和Nogo-B的相互作用是否能够影响乳腺癌细胞的增殖和迁移。本研究在三阴性乳腺癌（triple-negative breast cancer，TNBC）细胞中同时干预CD36与Nogo-B的表达来探索它们对细胞增殖与迁移的影响。结果表明在三阴性乳腺癌细胞中，单独抑制CD36或Nogo-B的表达都能够抑制细胞的增殖与迁移；同时抑制CD36与Nogo-B的表达时，这种抑制效果更加明显，且Vimentin、B细胞淋巴瘤-2（B-cell lympoma-2，BCL2）和增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）的表达受到抑制。在小鼠移植瘤模型中，E0771细胞转染CD36或Nogo-B的siRNA后成瘤能力降低；同时敲减CD36和Nogo-B时，肿瘤生长速度显著减慢。机制研究发现，抑制CD36和Nogo-B表达能够抑制脂肪酸结合蛋白4（fatty acid binding protein 4，FABP4）和脂肪酸转运蛋白4（fatty acid transport protein 4，FATP4） mRNA的含量，同时CD36和Nogo-B过表达刺激的细胞增殖被FABP4的siRNA降低，预示着抑制乳腺癌细胞中CD36与Nogo-B的表达可能通过抑制脂肪酸的吸收和转运而抑制细胞的生长和迁移。此外，抑制CD36与Nogo-B的表达可激活P53-P21-Rb信号通路，参与抑制CD36与Nogo-B表达而抑制的细胞增殖与迁移。本研究证明同时抑制CD36和Nogo-B的表达能够协同抑制三阴性乳腺癌细胞的增殖和迁移，为临床抗三阴性乳腺癌药物的开发提供了新的靶点。

Abstract:

Cluster of differentiation 36 (CD36) is a membrane glycoprotein receptor capable of binding and transporting fatty acid. Nogo-B regulates the metabolism of fatty acids in the liver and affects the development of liver cancer. To date, it remains unclear whether the interaction between CD36 and Nogo-B affects the proliferation and migration of breast cancer cells. In the current study, we aimed to determine whether the interference of CD36 and Nogo-B affects the proliferation and migration of triple-negative breast cancer (TNBC) cells. The results showed that inhibition of CD36 or Nogo-B alone can inhibit the proliferation and migration of TNBC cells, and the inhibitory effect was more pronounced when CD36 and Nogo-B were inhibited simultaneously. Meanwhile, it was found that inhibition of CD36 and Nogo-B expression can inhibit the expression of Vimentin, B-cell lympoma-2 (BCL2) and proliferating cell nuclear antigen (PCNA). In vivo, knockdown of CD36 or Nogo-B in E0771 cells reduced its tumorigenic ability, which was further enhanced by knockdown of CD36 and Nogo-B simultaneously. Mechanistically, inhibition of CD36 and Nogo-B expression can decrease fatty acid binding protein 4 (FABP4) and fatty acid transport protein 4 (FATP4) expression. Moreover, overexpression of CD36 and Nogo-B-induced cell proliferation was attenuated by FABP4 siRNA, indicating that inhibition of CD36 and Nogo-B expression could inhibit the absorption and transport of fatty acids, thereby inhibiting the proliferation and migration of TNBC. Furthermore, inhibition of CD36 and Nogo-B expression activated the P53-P21-Rb signaling pathway which contributed to the CD36 and Nogo-B-inhibited proliferation and migration of TNBC. Taken together, the results suggest that inhibition of CD36 and Nogo-B can reduce the proliferation and migration of TNBC, which provides new targets for the development of drugs against TNBC.