Circular RNA ZNF609 functions as a competing endogenous RNA in regulating E2F transcription factor 6 through competitively binding to microRNA-197-3p to promote the progression of cervical cancer progression

Abstract

Countless studies have demonstrated that Circular RNAs (circRNAs) exert vital effects in regulating tumorigenesis of various cancers. CircRNA ZNF609 (circ-ZNF609) has been reported as an oncogene in various human cancers. Nevertheless, its regulating effect in cervical cancer (CC) remains to be further explored. RT-qPCR was adopted to measure circ-ZNF609, miR-197-3p and E2F6 levels. CC cell proliferation, migration and invasion were analyzed via CCK-8 and transwell assays. Dual-luciferase reporter assay was adopted to confirm the interaction between miR-197-3p and circ-ZNF609 or E2F6. In the present study, it was found that circ-ZNF609 was elevated in CC tissues and cell lines, and circ-ZNF609 deletion repressed cell viability, migration and invasion in CC. Moreover, circ-ZNF609 was identified to negatively regulate miR-197-3p expression in CC cells. The inhibition of miR-197-3p abrogated the inhibitory effect on CC cell proliferation, migration and invasion induced by circ-ZNF609 knockdown. Additionally, we further demonstrated that circ-ZNF609 upregulated E2F6 by interacting with miR-197-3p. Finally, rescue assays indicated that E2F6 overexpression upended the suppression of CC progression induced by circ-ZNF609 deletion. In conclusion, circ-ZNF609 promoted CC progression through modulating the miR-197-3p/E2F6 axis as an oncogene. This finding offers a unique insight into CC molecular mechanism and suggests a potential target for CC therapy.

Circular RNA circ_0000228 promotes the malignancy of cervical cancer via microRNA-195-5p/ lysyl oxidase-like protein 2 axis

“…Circ_AKT1 accelerates CC progression by up-modulating AKT1 through miR-942-5p [ 21 ]. Circ-ZNF609 can promote the expression of E2F transcription factor 6 through competitively binding with miR-197-3p to facilitate the proliferation, migration and invasion of CC cells [ 22 ]. In this work, we identified that, circ_0000228, derived from ZEB1 transcript, which is transcribed from chromosome chr10:31661946–31676195, was up-regulated in CC tissues and cell lines.…”

Circular RNA circ_0001162 promotes cell proliferation and invasion of glioma via the miR-936/ERBB4 axis

“…The previous publications in Bioengineered also affirmed the involvement of circRNA/miRNA/mRNA axis in different tumors. For example, circ-LRP6 functioned as an oncogenic regulator in esophageal squamous cell carcinoma by targeting the miR-182/Myc signaling [ 37 ] and circ-ZNF609 facilitated the development of cervical cancer through the miR-197-3p-mediated E2F6 upregulation [ 38 ]. Also, circ_0000117 promoted cell proliferation and invasion in gastric cancer via regulating STAT3 expression by competitively binding to miR-337-3p [ 39 ].…”

Trichosanthin inhibits cervical cancer by regulating oxidative stress-induced apoptosis

“…Cervical cancer is globally among the dominant reasons for cancer-related deaths in females [24][25][26][27]. Evidence from clinical and experimental studies has shown that TCS has anti-tumor activity in a variety of anti-cancer treatments, including cervical cancer [16,28,29].…”