The lncRNA FENDRR inhibits colorectal cancer progression via interacting with and triggering GSTP1 ubiquitination by FBX8

作者：Jing Yang, Yuemei Hu, Zhenyu Tan, Feng Zhang, Wentao Huang, Kai Chen · 发表于：Heliyon · 年份：2023 · DOI：10.1016/j.heliyon.2023.e23161 · 被引用次数：10 · 研究领域：Cancer-related molecular mechanisms research、Circular RNAs in diseases、Cancer, Hypoxia, and Metabolism

Background: Colorectal cancer (CRC) is characterized by its aggressiveness and high fatality rate. Long noncoding RNAs (lncRNAs) as molecular scaffolding in CRC have received little attention. Methods: The TCGA database was used to find putative anti-oncogenic lncRNAs in CRC. The effect of FENDRR on CRC was evaluated using the colony formation assay, transwell assays, and wound healing assays, and FENDRR expression was validated by qRT-PCR. The location of the FENDRR binding proteins was determined by an RNA pull-down experiment, and the retrieved proteins were recognized by mass spectrometry. RNA immunoprecipitation (RIP) studies were used to demonstrate the interaction of GSTP1, FBX8, and FENDRR. Co-IP and immunofluorescence were utilized to confirm the connection between GSTP1 and FBX8. To determine the precise signaling pathways implicated in the action of FENDRR in CRC, we performed next-generation sequencing (NGS) on CRC cells transfected with a vector overexpressing FENDRR. Results: The expression of FENDRR was significantly downregulated in CRC tissue and cells. The results of the function experiments showed that overexpression of FENDRR reduced CRC cells' ability to proliferation, invasion, migration and tube formation. In terms of mechanism, FENDRR could bind both GSTP1 and FBX8, act as a molecular scaffold, and utilize FBX8 to regulate the stability of GSTP1's protein. Additionally, the outcomes of NGS and qRT-PCR demonstrated that the expression of genes linked to...