FXR1 modulates the expression of oncogenes and tumor suppressor genes associated with poor cancer prognosis

Abstract

Post-transcriptional regulation by RNA-binding proteins (RBPs) is critical for mRNA stability, localization, and translation, primarily through interaction with the 3’-untranslated region. Dysregulation of RBPs has been associated with various cancers, with fragile X-related protein 1 (FXR1) emerging as a critical RBP involved in tumorigenesis through its interactions with target mRNAs. Despite its significance, the specific role of FXRI in cancer progression remains underexplored. In this study, we investigated FXR1’s function using SH-SY5Y cells. RNA immunoprecipitation (RNA-IP) assay was employed to isolate RNA complexes associated with FXR1. We generated stable cell lines with either FXR1 overexpression or silencing to assess the impact of FXRI binding to mRNA complexes. Subsequent analyses, including quantitative reverse transcription polymerase chain reaction, correlation analysis, gene expression profiling, and survival analysis, were performed to validate the interactions of FXR1 with target mRNAs. Our RNA-IP analysis identified several mRNAs significantly enriched in FXR1-bound RNA complexes, including SHISAL1, SLC43A3, NBAT1, PDZK1IP1, ACKR3, KCNN3, NECAB2, ANO5, ATOH8, IGFBP7, LEMD1, GPR35, WNT7A, and F2RL3. Notably, we observed changes in the expression levels of these genes following FXR1 overexpression or depletion, indicating FXR1-mediated functional regulation. Co-expression analysis further supported FXR1’s association with these target mRNAs. These findings highlight the significant role of FXR1 in regulating the stability and expression of key mRNAs implicated in malignancies. The dysregulation of FXR1 and its interaction with these target transcripts suggest that FXR1 plays a critical role in tumor biology, potentially offering new avenues for therapeutic interventions. This study provides a deeper understanding of FXR1’s involvement in cancer and underscores the importance of RBPs in the post-transcriptional regulatory landscape of cancer progression.

Keywords

FXR1 / RNA immunoprecipitation / Carcinogenesis / Overexpression / Knockdown / Correlation analysis / Survival analysis

Funding

This work was supported by the National Natural Science Foundation of China (No.31371386) and the Natural Science Foundation of Henan Province (No.162300410042).

Conflict of interest

Xin-Ying Ji is an Editorial Board Member of this journal but was not involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

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