miR‑133b affects cell proliferation, invasion and chemosensitivity in renal cell carcinoma by inhibiting the ERK signaling pathway.

Renal cell carcinoma has the highest incidence rate of cancer types in the urinary system. Moreover, microRNAs (miRNA) have been closely associated with numerous types of tumor. The present study aimed to investigate the effects of miRNA (miR)‑133b on the proliferation, invasion and chemosensitivity of renal cell carcinoma cells, and to determine whether its mechanism was regulated by the ERK signaling pathway. Both renal cell carcinoma and adjacent healthy tissues from 60 patients, in addition to renal cell carcinoma lines, ACHN, Caki‑1, A‑498 and 786‑O, and 293 cells, were used in this study. miR‑133b expression was measured from renal cell carcinoma, adjacent healthy tissues and renal cell carcinoma cell lines by reverse transcription‑quantitative PCR. Cells were transfected with miR‑133b mimic to achieve miR‑133b overexpression. The proliferative, migratory and invasive ability of the cells were evaluated using MTT, wound healing and Matrigel assays, respectively, and flow cytometry was used to detect the apoptotic rate. Following treatment with an ERK inhibitor, U0126, and activator, LM22B‑10, western blotting was used to detect the expression of related proteins and the activity of the ERK signaling pathway. The overexpression of miR‑133b significantly inhibited cell proliferation, migration and invasion, whilst inducing apoptosis and increasing the drug sensitivity of renal cell carcinoma cells to cisplatin, docetaxel and doxorubicin. The miR‑133b mimic also increased the protein expression levels of Bax and decreased the expression levels of matrix metalloproteinase (MMP)‑2, MMP‑9, ATP‑binding cassette subfamily G2, P‑glycoprotein, Bcl‑2 and proliferating cell nuclear antigen, as well as the phosphorylation of ERK (P<0.05). The administration of the U0216 inhibitor demonstrated similar effects to miR‑133b overexpression, and there was no significant difference compared with the miR‑133b mimic transfection (P>0.05). However, the overexpression of miR‑133b combined with LM22B‑10 treatment weakened the anticancer effects of miR‑133b mimic transfection (P<0.05). In conclusion, miR‑133b overexpression was observed to inhibit the proliferation, migration and invasion of renal cell carcinoma cells and improve chemotherapeutic sensitivity; it was suggested that the mechanism maybe related to the inhibition of ERK1/2 phosphorylation and thus decreased ERK signaling pathway activity.

Molecular medicine reports. 2020 May 05 [Epub ahead of print]

Yuan Xu, Yuan Ma, Xiao-Ling Liu, Sheng-Li Gao

Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China., Department of Internal Medicine, School of Medicine, Shandong University, Jinan, Shandong 250100, P.R. China., Department of Clinical Medicine, Shandong Medical College, Jinan, Shandong 250021, P.R. China.