Circ-CCDC66 Upregulates REXO1 Expression to Aggravate Cervical Cancer Progression Via Restraining miR-452-5p

Abstract

BackgroundCervical cancer is one most common cancer types among females around the world. CircRNAs have been revealed to participate in multiple biological functions, and are involved in many diseases’ progression. In current study, we aimed to elucidate whether circ-CCDC66 participates cervical cancer progression. MethodsReal-time quantitative PCR (RT-qPCR) was conducted to measure the expression of circ-CCDC66, miR-452-5p, and REXO1 mRNA. Cell fractionation assay and RNA fluorescence in situ hybridization (FISH) were performed to locate circ-CCDC66 in cells. Cell proliferation ability was detected using cell account kit 8 (CCK-8). TRANSWELL assay was applied to evaluate cell migration or invasion ability. Bioinformatics analysis, biotinylated RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assays were conducted to assess the association between miR-452 and circ-CCDC66 or REXO1. Western blot was applied to measure the protein expression of REXO1. Animal tumor model was used to assess the effect of circ-CCDC66 in vivo.ResultsCirc-CCDC66 was upregulated in cervical cancer tumor tissues, and correlated with tumor stage and tumor size. Downregulation of circ-CCDC66 inhibited cervical cancer cell proliferation, migration, and invasion. Circ-CCDC66 was an efficient molecular sponge for miR-452-5p, and negatively regulated miR-452-5p expression. MiR-452 directly targeted REXO1. The effects of circ-CCDC66 on cervical cancer cells were functioned through miR-452-5p/REXO1 axis. In animal experiment, downregulation of circ-CCDC66 was found to suppress tumor growth in vivo.ConclusionOur results demonstrated the effects of circ-CCDC66/miR-452-5p/REXO1 axis in cervical cancer progression, we might provide a novel therapeutic target for cervical cancer.

CircCCDC66: Emerging roles and potential clinical values in malignant tumors

“…It plays a specific role in tumorigenesis and progression. This study shows that circCCDC66 competitively binds miR-452-5p through spongeization, and up-regulates REXO1 expression to aggravate the progression of cervical cancer (49). This may provide new insights into new therapeutic targets for basic research and clinical management of cervical cancer.…”

“…Recent studies have reported that circRNAs are abnormally expressed in cervical cancer and are important regulators of cervical cancer carcinogenesis and progression (83). Zhang et al (49) found that circCCDC66 was highly expressed in cervical cancer tissues (n=36, P<0.01). Knockdown of circCCDC66 attenuated the proliferation, migration, and invasion of cervical cancer cells in vitro and inhibited cervical cancer tumor growth in vivo.…”

“…Moreover, circCCDC66 was highly expressed in precancerous polyps and cancer tissues of colon cancer, and exacerbated the proliferation, migration and invasion of CRC cells by competitively binding miR-370 to upregulate MDM4 expression (15,47). And circCCDC66 could also exert oncogenic roles by binding miR-1238-3p and miR-452-5p in gastric and cervical cancers (19,49).…”

LINC01140 Targeting miR-452-5p/RGS2 Pathway to Attenuate Breast Cancer Tumorigenesis

“…It promotes cell proliferation, cell cycle transformation, and chemotherapy resistance, but inhibits apoptosis [18][19][20]. In contrast, however, miR-452-5p inhibits the development of prostate and cervical cancers [36,37]. These may be due to the heterogeneity of the cancers.…”