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Tumor Discovery Colorectal cancer: miRNA, mRNA, protein insights

nature of CRC tumors and the diverse cellular phenotypes Funding
within the tumor microenvironment. Importantly,
the correlations between mRNA and protein levels for This work was funded by Universities of Nottingham for
selected markers, including SMAD4, TGFBRII, BCL2, Mohammed Ilyas.
and RASA1, highlight the transcriptional regulation of Conflict of interest
protein expression in CRC. 17,36 These findings underscore
the importance of integrating multiple omics approaches The authors declare that they have no competing interests.
to comprehensively characterize the molecular landscape
of CRC. Author contributions
Although this study did not include functional Conceptualization: Hersh Ham-Karim, Mohammad Ilyas
validation experiments, the high correlation between Formal analysis: Hersh Ham-Karim, Alan Shwan
miRNAs and their target genes suggests that the selected Investigation: Hersh Ham-Karim, Narmeen Ahmad, Alan
miRNAs could play roles in CRC carcinogenesis by Shwan
regulating key signaling pathways. For example, the Methodology: Hersh Ham-Karim
inverse correlations between miR-21, miR-224, and Writing – original draft: Hersh Ham-Karim, Mohammad
TGFBRII highlight their role in suppressing TGFBRII Ilyas
expression, thus potentiating TGF-β signaling Writing – review & editing: Mohammad Ilyas
dysregulation in CRC. Similarly, the inverse associations Ethics approval and consent to participate
37
between miR-29a, miR-31, and RASA1 underscore
their regulatory role in modulating RASA1 expression, Access to tissues and ethics approval were granted by
consequently influencing Ras signaling pathway Nottingham Health Sciences Biobank, which has approval
activation in CRC. 14,38 In addition, the lack of correlation as an IRB from North West, Greater Manchester Central
between mRNA and protein levels of PTEN, coupled with Research Ethics Committee (REC reference: 15/NW/0685).
the strong correlation between miR-20a and reduced
PTEN protein expression, suggests that miR-20a may Consent for publication
regulate PTEN at the post-transcriptional level. These No patient consent was needed.
findings suggest that these miRNAs may play a role in
CRC tumorigenesis by modulating key tumor suppressor Availability of data
genes, although further mechanistic studies are required All datasets on which the conclusions of this paper rely
to confirm these interactions.
have been presented in the main manuscript and in the
This study has several strengths, such as the use supplementary file. In addition, raw data can be accessed
of matched tumor and normal mucosa tissues, which on request.
minimizes the influence of non-tumorous miRNAs.
However, there are also limitations, including the relatively References
small sample size, the lack of validation using alternative 1. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal
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5. Conclusion
doi: 10.5114/pg.2018.81072
Our findings suggest that upregulation of miR-20a, 2. Olivier T, Fernandez E, Labidi-Galy I, et al. Redefining
miR-21, miR-29a, and miR-31 may contribute to CRC cancer of unknown primary: Is precision medicine really
progression by targeting genes involved in key signaling shifting the paradigm? Cancer Treat Rev. 2021;97:102204.
pathways. While these miRNAs show potential as
diagnostic biomarkers, further research is needed to doi: 10.1016/j.ctrv.2021.102204
validate their clinical utility and explore their roles in CRC 3. Ždralević M, Raonić J, Popovic N, et al. The role of miRNA
pathways. Future studies should focus on investigating the in colorectal cancer diagnosis: A pilot study. Oncol Lett.
interactions between miRNAs, gene mutations, and other 2023;25(6):267.
CRC-related pathways to better understand the molecular doi: 10.3892/ol.2023.13853
mechanisms driving CRC.
4. Kim SM, Choi HS, Byun JS. Overall 5-year survival rate and
Acknowledgments prognostic factors in patients with stage IB and IIA cervical
cancer treated by radical hysterectomy and pelvic lymph
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Volume 4 Issue 1 (2025) 76 doi: 10.36922/td.4631