Circ_0000228 Promotes Cervical Cancer Progression Via Regulating MiR-337-3p/TGFBR1 Axis

Document Type : Original Article


1 Department of Gynecology and Obstetrics, Shengli Oilfield Central Hospital, Dongying, Shandong, China.

2 Department of Gynecology and Obstetrics, Shengli Oilfield Central Hospital, Dongying, Shandong, China


Objective: This study aims to investigate the biological function of circular RNA (circRNA) circ_0000228 in the cervical
cancer (CC).
Materials and Methods: In this experimental study, the GSE113696 dataset was downloaded from the Gene Expression
Omnibus (GEO). GEO2R was employed to obtain differentially expressed circRNA between CC tissues and matched paracancerous tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were employed to detect circ_0000228, microRNA-337-3p (miR-337-3p) and transforming growth factor, beta receptor I (TGFBR1) expression levels in the CC tissues and cells. Following gain-of-function and loss-of-function models establishment, CCK8 and BrdU tests were conducted to examine cell proliferation. Transwell experiment was executed to examine CC cells migration and invasion. A lung metastasis model was utilized to determine the ability of circ_0000228 on the lung metastasis. Bioinformatics analysis, dual-luciferase reporter experiment and RNA immunoprecipitation (RIP) assay were applied to verify the targeting relationship among miR-337-3p, circ_0000228, and TGFBR1.
Results: Circ_0000228 expression in the CC tissues and cells was up-modulated. Circ_0000228 overexpression markedly enhanced cell proliferation, migration, and invasion, while knocking down circ_0000228 remarkably repressed cell proliferation, migration, and invasion. MiR-337-3p could be adsorbed by circ_0000228. TGFBR1 was identified as a target gene of miR-337-3p that indirectly and positively modulated by circ_0000228 in the CC cells.
Conclusion: Circ_0000228 up-modulates TGFBR1 by targeting miR-337-3p to enhance CC cell proliferation, migration
and invasion. Also, Circ_0000228 is a promising therapeutic target for the CC.