Long non-coding RNA USP30-AS1 aggravates the malignant progression of cervical cancer by sequestering microRNA-299-3p and thereby over expressing PTP4A1

摘要

USP30 antisense RNA 1 (USP30-AS1) has been studied in bladder urothelial carcinoma. However, the detailed role of USP30-AS1 in cervical cancer remains to be elucidated. Therefore, the present study determined whether USP30-AS1 is implicated in cervical cancer malignancy, and investigated relevant molecular mechanisms. USP30-AS1 expression was measured via reverse transcription-quantitative PCR. Functional experiments, including the Cell Counting Kit-8 assay, flow cytometry, Transwell migration and invasion assays, and mouse tumour model, were performed in order to elucidate the roles of USP30-AS1. The target of USP30-AS1 was predicted using bioinformatics analysis, which was further verified via RNA immunoprecipitation and luciferase reporter assays. Herein, USP30-AS1 overexpression was detected in cervical cancer sample data from The Cancer Genome Atlas and our cohort. Patients with cervical cancer expressing high levels of USP30-AS1 exhibited shorter overall survival than those with low USP30-AS1 expression. In vitro and in vivo experiments revealed that USP30-AS1 interference promoted cell apoptosis; restrained cell proliferation, migration and invasion in vitro, and hindered tumour growth in vivo. Mechanistically, USP30-AS1 competed for microRNA-299-3p (miR-299-3p) in cervical cancer and lowered the regulatory actions of miR-299-3p on protein tyrosine phosphatase type IVA (PTP4A1), resulting in PTP4A1 overexpression. Furthermore, rescue experiments confirmed that miR-299-3p interventions or exogenous PTP4A1 could counteract the cancer-inhibiting actions of USP30-AS1 silencing on cervical cancer cells. In conclusion, the miR-299-3p/PTP4A1 axis is the downstream effector of USP30-AS1 in cervical cancer, forming the USP30-AS1/miR-299-3p/PTP4A1 pathway. This newly identified competing endogenous RNA pathway may offer a novel theoretical and experimental basis for developing promising new strategies for the targeted therapy of cervical cancer.