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Gene & Protein in Disease FXR1 modulates gene expression in cancer

Table 3. Summary of co‑expressed genes associated with FXR1 influence on a range of oncogenes, tumor suppressor
genes, and genes involved in cell cycle regulation.
Gene 1 Gene 2 Network group
Co‑expression Genetic Shared FXR1 has been identified as an overexpressed cancer
interaction protein promoter gene in various malignancies. Previous research
domains by Majumder et al. demonstrated FXR1’s regulation of
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FXR1 SLC43A3 0.0019075415 p21 and TERC RNA in oral squamous cell carcinoma,
PDZK1IP1 0.024462251 0.0005016976 where it contributes to the evasion of p53-induced
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ACKR3 0.020030404 0.0055209743 cellular senescence. Similarly, our findings highlight
KCNN3 0.030047113 0.0013293843 that FXR1 modulates the expression of key genes and
that the overexpression or silencing of FXR1 significantly
NECAB2 0.019942889 0.002363983 0.008422975 alters their transcriptional activity. In particular, the
ATOH8 0.00041934196 upregulation of FXR1 correlates with the overexpression of
IGFBP7 0.022652313 0.003947871 several oncogenes in cancer tissues, while its knockdown
LEMD1 0.00039458455 0.0019075415 leads to the repression of oncogenic targets. This direct
ANO5 0.041739117 modulation of gene expression by FXR1 suggests that it
GPR35 0.019942889 0.006434719 plays an integral role in the dysregulation of key cancer-
WNT7A 0.0008893441 0.006434719 related pathways.
F2RL3 0.002897449 0.0024557738 Our data support that FXR1 acts not only as a promoter
of oncogene expression but also regulates the degradation of
tumor suppressor mRNAs. This is consistent with previous
studies identifying RBPs, such as CPEB4 and HuR, as drivers
FXR1 activity, correlates with poorer prognosis, identifying of cancer progression through stabilization of oncogenic
them as potential biomarkers for cancer progression and transcripts in glioma and breast cancer, respectively. 31,32
candidates for therapeutic intervention. Furthermore, osteosarcoma cells exhibited elevated levels

Figure 7B and 7C illustrates that FXR1 is upregulated of the RBP Lin28A; its knockdown resulted in lower cell
in several cancers, reinforcing its potential involvement migration/invasion and proliferation while enhancing cell
in oncogenic pathways, particularly in regulating RNA death by stabilizing the lncRNA MALAT1. Fan et al.
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stability and translating key mRNAs. These findings align demonstrated that FXR1 controlled transcription and was
with previous studies that have identified FXR1 as a critical crucial for the progression of TP53/FXR2 homozygous
RBP associated with cancer development, highlighting its deletion-associated cancers in humans. Similarly, our
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importance as a potential therapeutic target in various study showed that FXR1 significantly alters the expression
malignancies. Further investigation into FXR1’s functional of both oncogenes and tumor suppressor genes, further
roles across different cancer types is warranted to supporting the hypothesis that FXR1 functions as a master
understand its contribution to tumorigenesis better. regulator of RNA metabolism in cancer. Specifically,
we have recently discovered that FXR1 overexpression
4. Discussion destabilizes PDZK1IP1 and ATOH8 mRNAs, thereby
Post-transcriptional regulation mechanisms play a pivotal promoting the progression of esophageal cancer.
role in gene expression, with RBPs frequently interacting Mechanistically, FXR1 directly interacts with the 3’UTRs
with target mRNA, particularly through their 3’UTR of PDZK1IP1 and ATOH8 transcripts, facilitating their
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regions. RBPs are central to regulating various events degradation and negatively regulating their expression.
in RNA metabolism, including splicing, translation, These findings highlight the oncogenic effects of FXR1
stability, transport, and degradation of mRNAs, as well through the PDZK1IP1/ATOH8 pathway, underscoring
as non-coding RNAs, such as circular RNAs, long non- its potential as a diagnostic or therapeutic target in cancer.
coding RNAs (lncRNAs), and miRNAs. These proteins In this study, the discovery that FXR1 regulates a diverse
form ribonucleoprotein complexes, thereby influencing set of genes, including oncogenes, such as SLC43A3,
gene expression through their interactions with specific ACKR3, KCNN3, LEMD1, GPR35, WNT7A, F2RL3, and
RNA targets. 5,27-30 Among RBPs, FXR1 has emerged as ANO5, as well as tumor suppressors, such as NBAT1,
a key player, modulating the stability and expression of PDZK1IP1, NECAB2, ATOH8, and IGFBP7, highlights its
numerous mRNAs involved in both physiological and significant role in cancer progression and patient prognosis.
pathological processes. Our study has revealed that FXR1, The observed correlations in this analysis underscore the
a known regulator of mRNA stability, exerts a significant functional role of FXR1 as a potential regulator of gene

Volume 4 Issue 1 (2025) 12 doi: 10.36922/gpd.5068