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 the HIF-1 pathway was down-regulated following FENDRR overexpression. Lastly, rescue tests demonstrated that overexpression of GSTP1 in CRC cells could completely restore the inhibition induced by FENDRR.Conclusion: In this study, we found that the molecular scaffolding protein FENDRR regulates the ubiquitination of GSTP1 and the suppression of the HIF-1 signaling pathway in the development of CRC. Our research provides more evidence of FENDRR's crucial role in the emergence of CRC and identifies it as a potential therapeutic target for CRC patients.
基金：
Science and Technology Commission of Changning District of Shanghai [CNKW2017Y09]
第一作者机构：[1]Soochow Univ, Dept Oncol, Affiliated Hosp 1, Suzhou 215006, Peoples R China[2]Shanghai Jiao Tong Univ, Tongren Hosp, Dept Pathol, Sch Med, 1111 Xianxia Rd, Shanghai 200336, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Yang Jing,Hu Yuemei,Tan Zhenyu,et al.The lncRNA FENDRR inhibits colorectal cancer progression via interacting with and triggering GSTP1 ubiquitination by FBX8[J].HELIYON.2023,9(12):doi:10.1016/j.heliyon.2023.e23161.
APA：
Yang, Jing,Hu, Yuemei,Tan, Zhenyu,Zhang, Feng,Huang, Wentao&Chen, Kai.(2023).The lncRNA FENDRR inhibits colorectal cancer progression via interacting with and triggering GSTP1 ubiquitination by FBX8.HELIYON,9,(12)
MLA：
Yang, Jing,et al."The lncRNA FENDRR inhibits colorectal cancer progression via interacting with and triggering GSTP1 ubiquitination by FBX8".HELIYON 9..12(2023)
