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.