Circ_0006646 Accelerates the Growth and Metastasis of Cervical Cancer by Elevating RRM2 Through miR-758-3p

摘要

Cervical cancer (CC) is the fourth most common cancer in women, and circular RNAs (circRNAs) have been shown to regulate CC development. However, the role of circ_0006646 in CC progression is still unclear. The levels of circ_0006646, miR-758-3p, and ribonucleotide reductase regulatory subunit M2 (RRM2) were evaluated by quantitative real-time PCR. Cell proliferation was tested by cell counting kit 8 and 5-ethynyl-2'-deoxyuridine assays. Flow cytometry was used to test cell apoptosis. Migration and invasion were estimated by transwell assay. Western blot assay was performed to examine protein expression. Dual-luciferase reporter assay, RIP assay, and RNA pull down assay were used to analyze the connection between miR-758-3p and circ_0006646 or RRM2. Tumor growth was detected by in vivo experiments. Exosomes were isolated form CC patients and healthy controls. Circ_0006646 expression was elevated in CC cells, and its knockdown suppressed CC cell growth, migration, and invasion. MiR-758-3p was sponged by circ_0006646, and RRM2 was targeted by miR-758-3p. In addition, the effects of circ_0006646 depletion on CC cell progression were overturned by miR-758-3p inhibitor, and either RRM2 overexpression reversed those effects of miR-758-3p overexpression on CC cell progression. Circ_0006646 was highly expressed in the exosomes of CC patients. Circ_0006646 expedited CC cell growth and metastasis by regulating miR-758-3p/RRM2 axis, and exosomal circ_0006646 might be a potential diagnostic indicator of CC.

关键词