Long non‑coding RNA USP30‑AS1 aggravates the malignant progression of cervical cancer by sequestering microRNA‑299‑3p and thereby overexpressing PTP4A1
Authors: Hongwei Chen
Limei Zhao
Mengyue Chen
Yugang Chi
Journal: Oncology Letters (2021)
Discipline: CLINICAL MEDICINE
Keywords: cervical cancer; competing endogenous RNA; microRNAs; non-coding RNA.
Affiliations: Department of Gynaecology, The First People's Hospital of Chongqing Liangjiang New Area, Chongqing 401120, P.R. China., Department of Gynaecology and Obstetrics, Chongqing Health Center for Women and Children, Chongqing 400021, P.R. China.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Here are multiple appearances of what seems to be the same well-traveled ruler, marked by a distinctive scratch just to the right of 2 . Different teams of researchers from six different institutions somehow used it to provide scale for the xenograft tumors in their studies. There would be no problem if all the images had been recorded at a single lab, but the papers do not mention outsourcing any of the experiments to an outside contractor. Upper row: - **Fig 7B from [Chen et al (2021)] **.  Representative images of subcutaneous tumours collected from the sh-USP30-AS1 and sh-NC groups. Rotated through 90 deg for ease of comparison. - Fig 8A from [Luo et al (2020)] .  Representative images of tumor xenografts originating from SW480 cells stably expressing sh-LINC00239 or sh-NC. Rotated through 90 deg. - Fig 7A from [Liu et al (2020)] .  Representative images of tumor xenografts that originated from SW480 cells stably overexpressing sh-VPS9D1-AS1 or sh-NC . ![file] Middle row: - Fig 7B from [He et al (2021)] .  At 31 days following cell injection, all mice were euthanized and tumor xenografts were resected and imaged . - Fig 6B from [Liu et al (2020)] .  All mice were euthanized at the end of the experiment, and the tumor xenografts were harvested and imaged . Rotated through 90 deg. - Fig 8A from [Yang, Yang Wang (2020)] .  Tumor growth curves were plotted according to the tumor volumes measured weekly . ![file] Lower row: - Fig 7B from [Li et al (2020)] .  Representative images of tumor xenografts collected from short hairpin RNA (sh)-LINC00525 and control (sh-NC) groups . - Fig 6A from [Dai et al (2020)] .  After 28 days post-inoculation, mice were euthanized and tumor xenografts were dissected and photographed . ![file] ,