Downregulation of hsa_circRNA_0001400 Helps to Promote Cell Apoptosis Through Disruption of the circRNA_0001400-miR-326 Sponge in Cervical Cancer Cells.

Yantao Cai,Fang Peng,Jiyan Su,Shuanghong Yin,Huiyi Liang,Chuansheng Yang,Chuyu Li,Chenglai Xia,Lin Li,Dixian Luo,Hui Liu,Anping Yang

doi:10.3389/fgene.2021.779195

Abstract

Background: In recent years, circular RNAs (circRNAs) have been reported to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of circRNAs in cervical cancer remain elusive. Methods: Flow cytometry assays were performed to measure cell apoptosis and cell cycle. Colony Formation and transwell chamber were performed to measure cell migration and invasion. Double luciferase reporter for gene analysis was used to detect the interaction between hsa-circRNA_0001400, miR-326, and Akt. Relative protein levels were determined by immunoblotting and relative gene levels were determined by quantitative real-time PCR. Tumor Xenograft Modeling was used to evaluate the effect of hsa_circRNA_0001400_siRNA in vivo. Results: In the present study, we showed that hsa_circRNA_0001400 was highly expressed in cervical cancer tissues relative to in matched normal tissue. We found that hsa_circRNA_0001400_siRNA significantly promoted the apoptosis of cervical cancer cells and arrested the cell cycle and migration of cervical cancer cells. We showed that hsa_circRNA_0001400_siRNA can inhibit the protein expression of Akt and that the inhibition of miR-326 could rescue the inhibition of Akt in cervical cancer cells. We found that has-miR-326 was downregulated in cervical cancer tissues and hsa_circRNA_0001400_siRNA could increase the gene expression of has-miR-326. We also observed that hsa_circRNA_0001400_siRNA inhibited the growth and angiogenesis of SiHa xenografts in nude mice. Conclusion: In conclusion, this study provides evidence that the hsa_circRNA_0001400–miR-326–Akt network promotes cervical cancer progression. Notably, our findings demonstrate the novel antitumor effects of hsa_circRNA_0001400_siRNA in cervical cancer.

Highlights

In recent years, circular RNAs have been reported to serve as essential regulators in several human cancers
In order to explore the role of circRNA in the pathogenesis of cervical cancer, we used an RNA sequencing method to search for differential circRNA
According to the classification results of biological processing, we found that these circRNAs are mainly involved in the apoptosis signal pathway through death receptors (Supplementary Figure S1A); according to the classification results of cellular components, these circRNAs mainly belong to the interleukin complex and protein kinase complex (Supplementary Figure S1B), while, according to the classification results from molecular function, these circRNAs mainly have binding functions (Supplementary Figure S1C)

Summary

Introduction

Circular RNAs (circRNAs) have been reported to serve as essential regulators in several human cancers. Infection by human papillomavirus (HPV) is a major cause of cervical cancer in women. Though HPV vaccines exist for the prevention of cervical cancer in women, they are still not widely available in developing countries and, as a result of the persistent lack of screening, a large number of cervical cancer cases in the 50 years can be expected (Wang et al, 2020). The 5-year survival rate is 100% with surgery and, in recent years, the incidence of cervical cancer has trended toward affecting women of youngers age, making the need to retain fertility a concern. There is an urgent need to clarify the mechanism of cervical cancer metastasis, develop new antitumor drugs, improve the quality of life of patients with cervical cancer, and improve the 5-year survival rate (Canfell, 2019)

Methods

Results

Discussion

Conclusion