Zhao Dongmei, Ma Yanying, Li Xu, Lu Xiaoyu
Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Henan Provincal Cancer Hospital, Zhengzhou, Henan, China.
J Cell Physiol. 2019 Sep;234(9):15429-15437. doi: 10.1002/jcp.28190. Epub 2019 Feb 26.
Fatty acid binding protein 4 (FABP4) is a novel tumor regulator that is abnormally expressed in many human cancers. In our study, upregulated microRNA-211 (miR-211) and reduced FABP4 expression were detected in colorectal cancer (CRC) patients and CRC cells. Mimic miR-211 or anti-miR-211 were transfected to investigate the effects of miR-211 on SW480 cells. The results showed that miR-211 promoted but anti-miR-211 inhibited cell migration, invasion, and epithelial-mesenchymal transition (EMT) of SW480 cells. Luciferase activity was decreased after cotransfection with miR-211 and WT-FABP4-UTR in SW480 cells. And reduced FABP4 protein expression by miR-211 indicated that FABP4 was the targeted gene of miR-211. miR-211 inhibited the activation of peroxisome proliferator-activated receptor (PPAR) γ, whereas overexpression of FABP4 reversed that effect. Finally, FABP4 inhibited the migration, invasion, and EMT of SW480 cells, whereas PPARγ agonist reversed the effects of FABP4. Thus, the miR-211/FABP4/PPARγ axis may be a novel target for CRC therapy.
脂肪酸结合蛋白4（FABP4）是一种新型肿瘤调节因子，在多种人类癌症中异常表达。在我们的研究中，在结直肠癌（CRC）患者和CRC细胞中检测到微小RNA-211（miR-211）上调和FABP4表达降低。转染模拟miR-211或抗miR-211以研究miR-211对SW480细胞的影响。结果表明，miR-211促进而抗miR-211抑制SW480细胞的迁移、侵袭和上皮-间质转化（EMT）。在SW480细胞中与miR-211和野生型FABP4-UTR共转染后，荧光素酶活性降低。miR-211导致FABP4蛋白表达降低，表明FABP4是miR-211的靶基因。miR-211抑制过氧化物酶体增殖物激活受体（PPAR）γ的激活，而FABP4的过表达逆转了这种作用。最后，FABP4抑制SW480细胞的迁移、侵袭和EMT，而PPARγ激动剂逆转了FABP4的作用。因此，miR-211/FABP4/PPARγ轴可能是CRC治疗的新靶点。
