circ_0067934 increases bladder cancer cell proliferation, migration and invasion through suppressing miR-1304 expression and increasing Myc expression levels

Exp Ther Med. 2020 Jun;19(6):3751-3759. doi: 10.3892/etm.2020.8648. Epub 2020 Apr 7.

Abstract

circRNAs have been demonstrated to be key regulators of bladder cancer progression. The present study aimed to investigate the effects of circular RNA (circ)_0067934 in bladder cancer progression. A total of 54 patients with primary bladder cancer were enrolled, and their tumor tissues and adjacent normal bladder tissues were collected. For in vitro functional assays, T24 cells were transfected with sicirc_0067934, and Cell Counting Kit-8 was used to analyze the proliferative capacity of T24 cells. In addition, Transwell and Matrigel assays were used to assess the cell migration and invasion abilities, and a dual-luciferase reporter assay was used to investigate the relationship between miR-1304 and circ_0067934. Finally, reverse transcription-quantitative PCR and western blotting were performed to analyze gene and protein expression levels, respectively. circ_0067934 expression levels were significantly increased in bladder cancer tissues (P<0.001), which was associated with metastasis and a significantly decreased 5-year overall (P<0.05) and disease-free survival (P<0.05). In vitro, T24 cells in the small interfering RNA (si)circ_0067934 group demonstrated significantly reduced proliferation, migration and invasion abilities compared with the si negative control (siNC) group (P<0.01). In addition, the knockdown of circ_0067934 directly increased microRNA (miR)-1304 expression levels in T24 cells. Myc was subsequently discovered to be directly inhibited by miR-1304 and circ_0067934 was observed to increase Myc expression levels in T24 cells through inhibiting miR-1304 expression levels (P<0.01). Compared with the siNC group and sicirc_0067934 + Myc overexpression group, T24 cells in the sicirc_0067934 group exhibited significantly decreased proliferative, migratory and invasive abilities (P<0.01). In conclusion, circ_0067934 was demonstrated to increase bladder cancer cell proliferation, migration and invasion through promoting Myc expression levels via the suppression of miR-1304 expression.

Keywords: Myc; bladder cancer; circular RNA_0067934; microRNA-1304; proliferation.