Research paperCirc-ATP8A2 promotes cell proliferation and invasion as a ceRNA to target EGFR by sponging miR-433 in cervical cancer
Introduction
Cervical cancer (CC) is a common gynecological carcinoma threatening women's life [Forouzanfar et al. 2011]. According to public reports, the incidence of CC is expected to reach 450,000 and it is estimated that 266,000 people would die of CC every year [Torre et al. 2015; Denny, 2012]. At present, first-line treatment for advanced CC is cytoreductive surgery supplemented with radiotherapy or chemotherapy. However, the majority of patients are at an advanced stage when diagnosed and lost the opportunity of operation [Pimple et al. 2016]. Thus, it is crucial to investigate the pathogenesis of CC and find effective interventions.
Circular RNAs (circRNAs) is a kind of RNA which has a closed loop and incapable to encode protein [Memczak et al. 2013]. In recent years, it has been proven to have important biological significance in cellular functions and disease development [Yao et al. 2017; Hu et al. 2019; Hall et al. 2018]. More and more circRNAs are reported to serve as drivers or inhibitors in the initiation of cancers including CC [Xu et al. 2019; Xu et al., 2018a, Xu et al., 2018b; Zhang et al., 2018a, Zhang et al., 2018b, Zhang et al., 2018c, Zhang et al., 2018d]. For instance, hsa_circ_0000263 takes part in CC progression via modulating miR-150-5p [Cai et al. 2018]. Additionally, circRNAs could sponge miRNAs and involved in the pathogenesis of CC [Liu et al. 2018]. For instance, enhanced expression of circ-0067934 facilitates CC progression by sponging miR-545 and thus elevating EIF3C expression [Hu et al. 2018]. Therefore, it is understandable that circRNA is a crucial factor in the pathogenesis of CC, which attracting widely attention from scholars.
Circ-ATP8A2 (hsa_circ_0100129), mapped to chr13:26116056–26,133,199, is a transcript production of ATP8A2 gene. The spliced sequence length of circ-ATP8A2 is 701 bp and this circRNA has not been studied before. It was found overexpressed in cervical cell lines compared with normal cells proved by high throughput microarray in the previous study [Ma et al. 2018]. In this project, we further evaluated its clinical value, functions and mechanisms in CC. Our study may provide clinical guidance for the treatment of CC.
Section snippets
Tissues collection
46 patients with CC was diagnosed and underwent surgery in our hospital. This project was authorized by the Ethics Committee of Qiqihar Medical University, and the pathological diagnosis for these CC samples was accomplished by two independent pathologists. The clinical tissues were preserved at −80 °C.
Cells and transfection
CC cells (HeLa, SiHa, C-33A and SW756) and HcerEpic used in our work were obtained from the Chinese Academy of Sciences (Shanghai, China) or preserved in our laboratory. All the cells were
Circ-ATP8A2 is overexpressed in CC tissues and cells and associated with poor prognosis
RT-qPCR was performed to assess circ-ATP8A2 expression in CC tissues, and the results uncovered that circ-ATP8A2 was dramatically increased in CC tissues than the noncancerous tissues (Fig. 1A). This result was further validated in four CC cells compared with HcerEpic cell line (Fig. 1B). These data suggested the upregulation of circ-ATP8A2 in CC and may contribute to the tumor initiation and development of CC. Furthermore, we divided the patients into two groups (high and low expression
Discussion
CC is a common cause of female carcinoma related deaths across the world. Due to its highly aggressive characteristics and existence of chemoresistance, the overall survival of CC is unfavorable [Forouzanfar et al. 2011; Torre et al. 2015]. Recent studies have reported that dysregulated expression of circRNAs in many cancers reflect disease progression and may predict patients curative effect [Li et al. 2018; Zhang et al., 2018a, Zhang et al., 2018b, Zhang et al., 2018c, Zhang et al., 2018d].
Conflict of interests
The authors report no competing interests exist in the present work.
Acknowledgement
The Project of Qiqihar Science and Technology Bureau (expression and clinical significance of PCNA and EGFR in different cervical lesions).
Author contributions
Conceived and designed the experiments: Hongtao Zhang; Performed the experiments: Lin Ding; Wrote the manuscript: Hongtao Zhang; Analyzed the data: Lin Ding.
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