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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
MicroRNA Biogenesis Pathway Genes Are Deregulated in Colorectal Cancer
Petra Vychytilova-Faltejskova1, Alena Svobodova Kovarikova2, Tomas Grolich3,4
1Central European Institute of Technology, Masaryk University, Kamenice 753/5, 62500 Brno, Czech Republic. vychytilova.petra@seznam.cz.
Abstract:
MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Each step of their production and maturation has to be strictly regulated, as any disruption of control mechanisms may lead to cancer. Thus, we have measured the expression of 19 genes involved in miRNAs biogenesis pathway in tumor tissues of 239 colorectal cancer (CRC) patients, 17 CRC patients with liver metastases and 239 adjacent tissues using real-time PCR. Subsequently, the expression of analyzed genes was correlated with the clinical-pathological features as well as with the survival of patients. In total, significant over-expression of all analyzed genes was observed in tumor tissues as well as in liver metastases except for LIN28A/B. Furthermore, it was shown that the deregulated levels of some of the analyzed genes significantly correlate with tumor stage, grade, location, size and lymph node positivity. Finally, high levels of DROSHA and TARBP2 were associated with shorter disease-free survival, while the over-expression of XPO5, TNRC6A and DDX17 was detected in tissues of patients with shorter overall survival and poor prognosis. Our data indicate that changed levels of miRNA biogenesis genes may contribute to origin as well as progression of CRC; thus, these molecules could serve as potential therapeutic targets.
Insights
Altered expression of microRNA (miRNA) biogenesis genes in colorectal cancer (CRC) tissues correlates with disease progression and patient survival. These miRNA pathway genes represent potential therapeutic targets for CRC.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs (miRNAs) are crucial regulators of gene expression, and their dysregulation is implicated in cancer development.
- Strict control over miRNA biogenesis is essential, as disruptions can lead to oncogenesis.
- Colorectal cancer (CRC) progression involves complex genetic alterations, including those affecting miRNA pathways.
Purpose of the Study:
- To investigate the expression levels of 19 genes involved in miRNA biogenesis in colorectal cancer tissues and adjacent normal tissues.
- To correlate the expression of these genes with clinical-pathological features and patient survival outcomes in CRC.
- To identify potential therapeutic targets within the miRNA biogenesis pathway for CRC treatment.
Main Methods:
- Real-time PCR was employed to quantify the expression of 19 miRNA biogenesis genes.
- Gene expression analysis was performed on tumor tissues (n=239), liver metastases (n=17), and adjacent normal tissues (n=239) from CRC patients.
- Statistical correlation analyses were conducted between gene expression, clinical-pathological parameters, and patient survival data.
Main Results:
- Significant overexpression of most miRNA biogenesis genes was observed in CRC tumor tissues and liver metastases compared to adjacent tissues, with exceptions like LIN28A/B.
- Deregulation of specific miRNA biogenesis genes correlated significantly with tumor stage, grade, location, size, and lymph node positivity.
- High expression of DROSHA and TARBP2 was linked to shorter disease-free survival; elevated XPO5, TNRC6A, and DDX17 levels correlated with reduced overall survival and poor prognosis.
Conclusions:
- Altered expression of miRNA biogenesis pathway genes is associated with the initiation and progression of colorectal cancer.
- Specific miRNA biogenesis genes demonstrate prognostic value, indicating their role in CRC patient outcomes.
- These dysregulated miRNA pathway genes represent promising novel therapeutic targets for colorectal cancer intervention.
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