Circ-DTL sponges miR-758-3p to accelerate cervical cancer malignant progression by regulating DCUN1D1 expression.

Abstract

Circular RNAs (circRNAs) play important roles in regulating various cancer progression. However, the function and clinical significance of circ-denticleless E3 ubiquitin proteinligase homolog (DTL) in cervical cancer (CC) have not been studied. The present work explored the function and mechanism of circ-DTL in CC development.Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of circ-DTL, miR-758-3p, and DCUN1D1. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. Cell cycle and cell apoptosis were investigated by flow cytometry. Wound-healing assay and transwell assay were conducted to assess cell migration and cell invasion. Western blot assay was carried out to determine protein expression. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to identify the relationship between miR-758-3p and circ-DTL or DCUN1D1. Xenograft mouse model assay was conducted to explore the role of circ-DTL in CC progression in vivo. Circ-DTL and DCUN1D1 expression were upregulated in CC tissues and CC cells, but miR-758-3p expression was downregulated. Knockdown of circ-DTL inhibited CC cell growth, migration, and invasion and promoted cell cycle arrest and cell apoptosis. Circ-DTL could sponge miR-758-3p to modulate CC cell progression. Moreover, miR-758-3p inhibited CC malignant development by suppressing DCUN1D1 expression. In addition, circ-DTL knockdown repressed CC cell tumor properties in vivo.Circ-DTL acted as a tumor promoter in CC development by regulating the miR-758-3p/DCUN1D1 pathway.