Circ-ABCB10 knockdown inhibits the malignant progression of cervical cancer through microRNA-128-3p/ZEB1 axis

Wei Feng,Dongya Zhang,Ruitao Zhang

doi:10.1186/s12575-021-00154-8

Wei Feng, Dongya Zhang + Show 1 more

Open Access

https://doi.org/10.1186/s12575-021-00154-8

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Abstract

AimsWe focused on the detailed functions of circ-ABCB10 in cervical cancer (CC) development and its mechanisms.BackgroundThe increasing findings have proposed the central roles of circular RNAs (circRNAs) in the tumorigenesis of various human cancers. Circ-ABCB10 displays promising oncogenic effect in several tumors.MethodsCirc-ABCB10 and miR-128-3p production levels in CC tissues and cells were tested through RT-qPCR. The association of circ-ABCB10 expression with clinicopathologic parameters of CC patients was statistically analyzed. Cell proliferation, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) were evaluated by MTT, transwell invasion assays, flow cytometry analyses, and western blot examination of EMT markers. The binding activity between miR-128-3p and circ-ABCB10 or zinc finger E-box binding homeobox 1 (ZEB1) was explored through pull-down assay or luciferase reporter assay. The influence of circ-ABCB10 on CC tumorigenesis was evaluated by in vivo xenograft experiments.ResultsThe elevated circ-ABCB10 expression was determined in CC tissues and cells. Moreover, higher production level of circ-ABCB10 was close related to lymph-node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, and tumor size in CC patients. Loss of circ-ABCB10 weakened cell proliferative and invasive abilities, inhibited EMT, and induced apoptosis in CC. Loss of circ-ABCB10 inhibited ZEB1 expression by serving as a sponge of miR-128-3p in CC cells. Circ-ABCB10 sponged miR-128-3p to enhance cell proliferation, invasion, EMT and inhibit apoptosis in CC cells. Xenograft tumor assays confirmed that circ-ABCB10 knockdown inhibited CC tumor growth.ConclusionOur study suggests that circ-ABCB10 depletion inhibits proliferation, invasion and EMT and promotes apoptosis of cervical cancer cells through miR-128-3p/ZEB1 axis and represses CC tumor growth.

Highlights

The increasing findings have proposed the central roles of circular RNAs in the tumorigenesis of various human cancers
Higher production level of circ-ABCB10 was close related to lymph-node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, and tumor size in CC patients
Our study suggests that circ-ABCB10 depletion inhibits proliferation, invasion and epithelial-mesenchymal transition (EMT) and promotes apoptosis of cervical cancer cells through miR-128-3p/zinc finger E-box binding homeobox 1 (ZEB1) axis and represses CC tumor growth

Summary

Introduction

The increasing findings have proposed the central roles of circular RNAs (circRNAs) in the tumorigenesis of various human cancers. Cervical cancer (CC), a huge threat to female health and life, accounts for more than 3% of all new cancer diagnoses and the total cancer deaths worldwide [1]. The morbidity and mortality of CC patients rank the fourth in all malignancies [1]. It was estimated that over 569,000 new CC cases and 311,000 CC-related deaths occurred in 2018 globally [1]. The incidence rate and mortality of CC are higher in low-income and middle-income countries (LMIC) relative to developed countries due to the limitations in the management of CC in LMIC [2, 3]. To better control CC, it is imperative to deeply investigate the vital molecular events implicated in CC tumorigenesis and progression [5]

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