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Updated: May 25, 2026
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Published on: October 27, 2020
Altered miRNA expression patterns in Tff2 knock-out mice correlate with cellular pathways of neoplastic
Aftab Ali Shah1, Petra Leidinger, Andreas Keller
1Division of Molecular Genetics, Institute of Human Genetics, University of Tübingen, Wilhelmstr. 27, D-72074 Tübingen, Germany. aftabalishah1@gmail.com
Abstract:
The trefoil peptide family, consisting in mammals of three members namely TFF1, 2 and 3, plays a cytoprotective role in epithelial cells of various tissues, mainly in the digestive tract. Tff1, Tff2 or Tff3 knock-out mouse models developed various kinds of gastrointestinal impairment. microRNAs are known to be novel gene regulators. We aimed to investigate the physiological role of such miRNAs in Tff2 knock-out mice. Whole miRNome profiling and in silico analysis were performed for Tff2-KO and WT mice. Our latest data explored the role of miRNAs in the regulatory cascades and molecular processes of Tff2-/- mice. As much as 6% of the Tff2-KO mice miRNome was significantly dys-regulated. Further in silico analysis suggests that the respective dys-regulated part of the miRNome is involved in human pathological processes, including pancreatic, colorectal and basal cell cancer. Additionally, the dys-regulated miRNome targets pathways involved in carbohydrate metabolism and adipocytokine signaling. The latter links deficient caloric maintenance in Tff2 and previous observation in Tff3-KO mice with miRNAs. In summary, our proof-of-concept study indicates that miRNAs may play an important role in the regulatory processes of the trefoil peptide family, especially in the regulation of cancer-related cascades.
Insights
Trefoil factor 2 (TFF2) deficiency impacts microRNAs (miRNAs), altering pathways linked to gastrointestinal health and cancer. This study reveals miRNAs as key regulators in TFF2
Area of Science:
- Molecular Biology
- Genetics
- Gastroenterology
Background:
- Trefoil peptides (TFF1, TFF2, TFF3) are crucial for epithelial cell protection, particularly in the digestive tract.
- TFF2 knockout mice exhibit gastrointestinal impairments, suggesting a role in maintaining tissue homeostasis.
Purpose of the Study:
- To investigate the physiological role of microRNAs (miRNAs) in TFF2 knockout mice.
- To identify dysregulated miRNAs and their target pathways in the absence of TFF2.
Main Methods:
- Whole miRNome profiling was conducted on TFF2 knockout (TFF2-KO) and wild-type (WT) mice.
- In silico analysis was employed to predict miRNA targets and associated biological pathways.
Main Results:
- Approximately 6% of the miRNome was significantly dysregulated in TFF2-KO mice compared to WT.
- In silico analysis indicated that dysregulated miRNAs target pathways implicated in pancreatic, colorectal, and basal cell cancers.
- Affected pathways include carbohydrate metabolism and adipocytokine signaling, potentially linking TFF2 deficiency to caloric maintenance issues.
Conclusions:
- MicroRNAs play a significant role in the regulatory network of the trefoil peptide family, particularly TFF2.
- Dysregulated miRNAs in TFF2 deficiency are associated with cancer-related pathways and metabolic signaling.
- This study provides a foundation for understanding miRNA involvement in TFF peptide function and associated pathologies.
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