MiR-375 Affects the Proliferation, Invasion, and Apoptosis of HPV16-Positive Human Cervical Cancer Cells by Targeting IGF-1R

Abstract

Objective The aim of this study was to examine the relationship between miR-375 expression and the proliferation, apoptosis, and migration of cervical cancer cells. To further explore the potential target gene of miR-375, insulin-like growth factor 1 receptor (IGF-1R) was detected in miR-375 overexpressed and inhibited cervical cancer cells, which clarified the potential mechanism of miR-375 in the growth and development of cervical cancer. Methods In a cervical cancer cell line (Caski), miR-375 overexpression and knockdown were achieved by transfection with a synthetic miR-375 mimic or miR-375-targeting inhibitor oligonucleotides, respectively, using siRNA-Mate transfection reagents. Real-time Polymerase Chain Reaction was performed to detect the expression level of miR-375. The functional effects of miR-375 on cell proliferation, migration, and apoptosis were evaluated using a Cell Counting Kit (CCK-8) and through scratch wound tests and apoptosis assays, respectively. Western blotting was performed to detect the expression level of the IGF-1R protein. Result Transfection with the miR-375 mimic significantly upregulated the expression of miR-375 by approximately 7.76-fold (P < 0.05), reduced cell proliferation and migration (P < 0.05), increased apoptosis (P < 0.05), and decreased the expression of the IGF-1R protein by 24.73% (P < 0.05) compared with the negative control. In contrast, transfection of the miR-375 inhibitor decreased the expression of miR-375 by 14.39% (P < 0.05), significantly increased cell proliferation and migration (P < 0.05), significantly reduced the cell apoptosis (P < 0.05), and upregulated the expression of the IGF-1R protein by 2.29-fold (P < 0.05). The cells transfected with the negative control showed no significant changes compared with the blank control for each parameter (P > 0.05). Conclusions miR-375 plays an important role in the tumorigenesis and development of cervical cancer. IGF-1R might represent a target gene of miR-375 in cervical cancer.