EFFECTS OF RAB27 ON THE PROLIFERATION AND INVASION OF BLADDER CANCER CELLS BY REGULATING NF-ΚB AND FAK SIGNALING PATHWAY ACTIVITY AND CYCLIN

Nannan Yang¹, Xiaopeng Zhang², Qiaoyan Wu³, Faren Xu^{4, *}

¹Chongqing Medical University, Shaoxing, PR China - ²Nanjing Medical University, Nanjing, PR China - ³School of Medicine, Nanhu University, Jiaxing University, Jiaxing, PR China - ⁴Shaoxing Health School, Shaoxing, PR China

Objective: To study the effects of Rab27 on the proliferation and invasion of bladder cancer cells by regulating the activity of nuclear transcription factor-κB (NF-κB) and focal adhesion kinase (FAK) signalling pathways and cyclin. 

Methods: Cancer tissues from 12 bladder cancer patients who underwent surgical treatment in our hospital from April 2017 to February 2019 were selected. At the same time, normal tissues adjacent to the cancer were selected for comparison. Immunohistochemistry was used to test the expression levels of Rab27 in bladder cancer tissue and normal tissue adjacent to the cancer. Cells from the human bladder cancer cell line BIU-87 were transfected with the Rab27 overexpression plasmid, and cells from human bladder cancer cell line 5637 were transfected with the Rab27-specific siRNA; a negative control group was prepared. The expression levels of Rab27 in BIU-87 and 5637 cells were determined by Western blotting and RT-PCR. Cell proliferation was detected by CCK-8. Transwell cells were used to determine the change in invasion ability of BIU-87 and 5637 cells. The expression levels of apoptosis-related proteins Caspase-3, poly (ADP-ribose) polymerase (PARP), Bcl-2, p-IκB, p-p65 and p-FAK, and cyclins CyclinE and CyclinD1 were tested by Western blot. 

Results: The expression level of Rab27 in bladder cancer tissue was significantly higher than that in normal tissues adjacent to the cancer. In BIU-87 cells in the RAB27 overexpression group, the expression levels of Rab27, apoptosis-related proteins, p-IκB, p-p65, p-FAK, CyclinE and CyclinD1 were significantly increased compared to the control group, and proliferation and invasion ability were significantly enhanced (P<0.05). In 5637 cells in the siRab27 group, the expression levels of Rab27, apoptosis-related proteins and p-IκB, p-p65, p-FAK, CyclinE and CyclinD1 were significantly decreased compared to the control group, and cell proliferation and invasion ability were significantly reduced (P<0.05). 

Conclusion: Rab27 may upregulate the expression of CyclinE and CyclinD1 by activating NF-κB and FAK signalling pathway activities to promote the proliferation and invasion of bladder cancer cells.