MIR-200B AFFECTS THE PROLIFERATION, MIGRATION AND INVASION OF BREAST CANCER CELLS BY REGULATING THE PI3K/AKT SIGNALING PATHWAY THROUGH THE REGULATION OF FUT4

Ning Li¹, Zhidong Shan¹, Peng Zhou¹, Sheng Lv^{2, *}

¹Department of Two Branches Outside, The First People’s Hospital of Yongkang, Yongkang, PR China - ²Department of Two Branches Outside, Jinhua Rehabilitation Hospital, Jinhua, PR China

Objective: To analyze the effect of microRNA-200b (miR-200b) on the proliferation, migration and invasion of breast cancer cells by regulating the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway through the regulation of fucosyltransferase 4 (FUT4). 

Methods: 35 cases of breast cancer tissues and adjacent normal tissues were randomly selected for surgical treatment in our hospital, and the expressions of miR-200b and FUT4 in breast cancer tissues and adjacent normal tissues were determined by real-time quantitative PCR. Human breast cancer cells (MCF-7) were cultured and transfected to obtain overexpressed miR-200b (miR-200b overexpressed group) and control cells (control group). Real-time quantitative PCR was used to determine the expression of miR-200b and FUT4 in the control group and the miR-200b overexpression group. Cell proliferation in each group was determined by CCK-8 and clonogenesis assay. The cell migration ability of each group was determined by scratch test. Transwell cell invasion assay was used to determine the change of cell invasion ability in each group. The expression of PI3K and Akt in each group was determined by western blot. 

Results: Compared with normal adjacent tissues, the expression level of miR-200b in breast cancer tissues was significantly decreased, and the expression level of FUT4 was significantly increased (P<0.01). Compared with the control group, the expression level of miR-200b was significantly increased in the miR-200b overexpression group, and the expression level of FUT4 was significantly decreased (P<0.05). With the extension of time, both groups of cells showed an upward trend. There was no significant difference in cell proliferation capacity between the two groups at 1d and 2d (P>0.05). Starting from the 3rd day, the proliferation capacity of cells in the miR-200b overexpression group was significantly lower than that in the control group (P<0.05 or P<0.01). Compared with the control group, the miR-200b overexpression group had significantly reduced cell clone formation, migration ability, invasion ability, and PI3K and Akt expression levels (P<0.05). 

Conclusion: miR-200b may inhibit the activation of PI3K/Akt signaling pathway by down-regulating FUT4 expression, thereby inhibiting the proliferation, migration and invasion of breast cancer cells.