E2F1-induced PTPRG-AS1 inhibits radiosensitivity by targeting the miR-670-3p/SYPL1 axis in colorectal cancer
Year: 2025
Type: article
Abstract: Background Colorectal cancer (CRC) is a main cause of cancer-related mortality, and radiotherapy remains a critical therapeutic method for CRC patients. Accumulating evidence indicates that lncRNAs are involved in the development of radioresistance in various cancers, including CRC. This study investigates the functional role and underlying mechanisms of the lncRNA PTPRG-AS1 in CRC. Methods Radioresistant CRC cell lines were established by exposing HCT-116 and SW480 cells to daily irradiation of 2 Gy for 7 consecutive days. PTPRG-AS1 expression in CRC tissues and cells was detected using RT-qPCR. Its effects on cell survival, proliferation, apoptosis, and migration were measured by colony formation, EdU, flow cytometry, and Transwell assays, respectively. Molecular interactions were analyzed using chromatin immunoprecipitation (ChIP), RNA pulldown, luciferase reporter, and RNA immunoprecipitation (RIP) assays. After establishment of Xenograft mouse models and irradiation, tumor volume and weight were calculated. Ki67 immunofluorescence staining was performed to assess tumor cell proliferation. Results PTPRG-AS1 exhibited high levels in parental and radiation-resistant CRC cells. Silencing of PTPRG-AS1 suppressed cell growth, migration, and tumor growth while increasing radiosensitivity and apoptosis. Furthermore, E2F1-inudced PTPRG-AS1 functioned as a ceRNA by sequestering miR-670-3p, thereby upregulating SYPL1 expression. Rescue experiments manifested that the inhibitory effects of PTPRG-A S1 depletion on CRC cell progression and radioresistance were reversed by miR-670-3p inhibition or SYPL1 overexpression. Conclusion E2F1-induced PTPRG-AS1 targets the miR-670-3p/SYPL1 axis to promote CRC cellular process and radioresistance.
Authors: Jie Cheng, Jingru Chen, Yang Liu
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,400
OpenAlex ID: W4414498024