Page 147 - GPD-4-1

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
FXR1 modulates the expression of oncogenes

and tumor suppressor genes associated with
poor cancer prognosis

Faiz Ali Khan 1,2,3,4 * , Xin-Ying Ji * , Shaoping Ji * , and
5,6
4,6
1,2
Jingcheng Dong *
1 Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
2 Institutes of Integrative Medicine, Fudan University, Shanghai, China
3 Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and
Research Centre (SKMCH&RC), Lahore, Punjab, Pakistan
4 Laboratory of Cell Signal Transduction, Department of Biochemistry and Molecular Biology, School
of Basic Medical Sciences, Henan University, Kaifeng, Henan, China
5 Department of Medicine, Huaxian County People’s Hospital, Huaxian, Henan, China
6 Center for Molecular Medicine, Faculty of Basic Medical Subjects, Shu-Qing Medical College of
Zhengzhou, Zhengzhou, Henan, China

*Corresponding authors:
Faiz Ali Khan Abstract
(faizalikh@fudan.edu.cn);
Jingcheng Dong Post-transcriptional regulation by RNA-binding proteins (RBPs) is critical for mRNA
(jcdong2004@126.com); stability, localization, and translation, primarily through interaction with the
Shaoping Ji
(shaopingji@henu.edu.cn); 3’-untranslated region. Dysregulation of RBPs has been associated with various
Xin-Ying Ji cancers, with fragile X-related protein 1 (FXR1) emerging as a critical RBP involved in
(10190096@vip.henu.edu.cn) tumorigenesis through its interactions with target mRNAs. Despite its significance, the
Citation: Khan FA, Ji X, Ji S, specific role of FXRI in cancer progression remains underexplored. In this study, we
Dong J. FXR1 modulates the investigated FXR1’s function using SH-SY5Y cells. RNA immunoprecipitation (RNA-IP)
expression of oncogenes and assay was employed to isolate RNA complexes associated with FXR1. We generated
tumor suppressor genes associated
with poor cancer prognosis. Gene stable cell lines with either FXR1 overexpression or silencing to assess the impact of
Protein Dis. 2025;4(1):5068. FXRI binding to mRNA complexes. Subsequent analyses, including quantitative reverse
doi: 10.36922/gpd.5068 transcription polymerase chain reaction, correlation analysis, gene expression profiling,
Received: October 7, 2024 and survival analysis, were performed to validate the interactions of FXR1 with target
1st revised: December 3, 2024 mRNAs. Our RNA-IP analysis identified several mRNAs significantly enriched in FXR1-
2nd revised: December 12, 2024
3rd revised: December 27, 2024 bound RNA complexes, including SHISAL1, SLC43A3, NBAT1, PDZK1IP1, ACKR3, KCNN3,
4th revised: December 31, 2024 NECAB2, ANO5, ATOH8, IGFBP7, LEMD1, GPR35, WNT7A, and F2RL3. Notably, we observed
Accepted: January 3, 2025 changes in the expression levels of these genes following FXR1 overexpression or
Published online: February 5,
2025 depletion, indicating FXR1-mediated functional regulation. Co-expression analysis
further supported FXR1’s association with these target mRNAs. These findings highlight
Copyright: © 2025 Author(s).
This is an Open-Access article the significant role of FXR1 in regulating the stability and expression of key mRNAs
distributed under the terms of the implicated in malignancies. The dysregulation of FXR1 and its interaction with these
Creative Commons Attribution target transcripts suggest that FXR1 plays a critical role in tumor biology, potentially
License, permitting distribution,
and reproduction in any medium, offering new avenues for therapeutic interventions. This study provides a deeper
provided the original work is understanding of FXR1’s involvement in cancer and underscores the importance of
properly cited. RBPs in the post-transcriptional regulatory landscape of cancer progression.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: FXR1; RNA immunoprecipitation; Carcinogenesis; Overexpression;
regard to jurisdictional claims in
published maps and institutional Knockdown; Correlation analysis; Survival analysis
affiliations.

Volume 4 Issue 1 (2025) 1 doi: 10.36922/gpd.5068