CircAGFG1 promotes cervical cancer progression via miR-370-3p/RAF1 signaling

Abstract

BackgroundIn past decades, circular RNAs (circRNAs) have achieved increasing attention because of its regulatory role in different kinds of cancers. However, how circAGFG1 regulates cervical cancer (CC) is still largely undiscovered. This study aims to evaluate the role of a novel circRNAs and related molecular mechanism in CC cells.MethodsHigh or low level of circAGFG1 was detected in CC cells or normal cell line with qRT-PCR. The proliferative and migratory abilities of CC cells were assessed with loss-of function assays. The downstream miRNA and mRNA of circAGFG1 were searched out and proved by using bioinformatics analysis and mechanism experiments. Recue assays were designed to confirm the role of circAGFG1/miR-370-3p/RAF1 axis in CC cell activities.ResultsThe levels of circAGFG1 was abundant in CC cells in comparison with normal cervical cell End1/E6E7. The inhibitory effect of decreased circAGFG1 level on the proliferative and migratory abilities of CC cells was assessed. CircAGFG1 and miR-370-3p were localized in the cytoplasm and they can interact with each other. Moreover, miR-370-3p was downregulated in CC cells. We also determined the negative effect of miR-370-3p on RAF1. CircAGFG1 could promote RAF1 expression by absorbing miR-370-3p, thereby activating RAF/MEK/ERK pathway. circAGFG1 promoted proliferation and migration of CC cells via enhancing the activity of RAF/MEK/ERK pathway by sponging miR-370-3p and further regulating RAF1.ConclusionThe results of this study provided new evidence that circAGFG1 acted as a vital regulator in cervical cancer proliferation and migration, giving great promise to apply it as a potential biomarker for diagnosis and therapy in CC treatment.

TCEB3 is Regulated by Circ-0000212/miR-140-3p Axis to Promote the Progression of Cervical Cancer

“… 41 Wu et al indicated that circAGFG1 promoted proliferation and migration of cervical cancer cells via miR-370-3p/RAF1 signaling. 42 Based on these findings, we found that miR-140-3p was directly regulated by circ-0000212 by RIP and dual-luciferase reporter assays. As we have seen, circ-0000212 (genomic location: chr10: 7405839–7423911) is a new circRNA in cervical cancer.…”

A Novel Circulating MiRNA-Based Signature for the Diagnosis and Prognosis Prediction of Early-Stage Cervical Cancer

“…Wu and Zhou reported that circAGFG played an oncogenic role in CC by absorbing miR-370. In addition, the expression of miR-370 was significantly reduced in GC cells, 21 suggesting that miR-370 might act as a tumor suppressive miRNA in CC.…”

The Expression, Functions and Mechanisms of Circular RNAs in Gynecological Cancers

“…The RAF/MEK/ERK cascade plays a critical role in the development and progression of cancer [109]. A recent study suggested that circAGFG1 was upregulated in CC cell lines compared with normal cervical cells, and it could induce CC cell proliferation and migration by elevating RAF1 expression and activating the MEK/ERK pathway, via sponging miR-370-3p (a suppressor of RAF1) [93]. Epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells acquire mesenchymal phenotypes, thus conferring the malignant properties to cancer cells including invasive behaviors, cancer stem cell properties, and greater resistance to cancer treatment [110].…”

“…High-risk subtypes (16 and 18) of human papillomavirus (HPV) are well established as the causative agents responsible for CC [ 69 ]. Massive studies have shown that a large number of circRNAs were differentially expressed in CC tissues compared with adjacent normal cervical tissues, and play oncogenic or tumor-suppressive roles in the initiation and progression of CC [ 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 ]. All of the circRNAs that are abnormally expressed in CC are summarized in Table 1 , and their functions in CC are shown in Figure 3 .…”