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Published on: November 15, 2024
The non-coding RNome after splenectomy
Mihnea P Dragomir1,2, Stefan Tudor2, Keishi Okubo1
1Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
Splenectomy is a common surgical procedure performed in millions of people worldwide. Epidemiologic data show that splenectomy is followed by infectious (sepsis) and non-infectious complications, with unknown mechanisms. In order to explore the role of the non-coding transcripts involved in these complications, we analysed a panel of circulating microRNAs (miRNAs), which were previously reported to be deregulated in sepsis, in the plasma of splenectomized patients. MiR-223 was overexpressed immediately and late after splenectomy, while miR-146a was overexpressed immediately after splenectomy, returning latter to basal levels; and miR-16, miR-93, miR-26a and miR-26b were overexpressed only late after splenectomy, suggesting similarities with sepsis. We also explored the non-coding (nc)RNome of circulating peripheral blood leucocytes by performing a ncRNA full genome profiling. We observed a reorganization of the ncRNoma after splenectomy, characterized by up-regulation of miRNAs and down-regulation of transcribed pyknons (T-PYKs). Pathway analysis revealed that deregulated miRNAs control pathways involved in immunity, cancer and endothelial growth. We checked the expression of the ncRNAs in 15 immune cell types from healthy donors and observed that plasma miRNAs, cellular miRNAs and T-PYKs have a cell-specific expression pattern and are abundant in different types of immune cells. These findings suggest that the ncRNAs potentially regulate the immune changes observed after splenectomy.
Insights
Splenectomy alters circulating non-coding RNAs (ncRNAs), including microRNAs (miRNAs), potentially explaining post-surgical complications. These ncRNAs show cell-specific expression and regulate immune pathways.
Area of Science:
- Immunology
- Molecular Biology
- Genomics
Background:
- Splenectomy is a common procedure with known infectious and non-infectious complications.
- The underlying mechanisms of these complications, particularly involving non-coding RNAs, remain largely unknown.
Purpose of the Study:
- To investigate the role of circulating non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), in post-splenectomy complications.
- To analyze the global ncRNA profile in leukocytes following splenectomy.
Main Methods:
- Analysis of circulating plasma miRNAs in splenectomized patients.
- Genome-wide profiling of non-coding RNAs (ncRNAs) in peripheral blood leukocytes.
- Pathway analysis of deregulated ncRNAs.
- Cell-specific expression analysis of ncRNAs in 15 immune cell types.
Main Results:
- Specific miRNAs (miR-223, miR-146a, miR-16, miR-93, miR-26a, miR-26b) showed altered expression post-splenectomy, with some patterns resembling sepsis.
- Splenectomy induced a reorganization of the leukocyte ncRNome, with increased miRNAs and decreased transcribed pyknons (T-PYKs).
- Deregulated miRNAs target pathways crucial for immunity, cancer, and endothelial growth.
- Plasma and cellular ncRNAs exhibit cell-specific expression patterns within immune cells.
Conclusions:
- Circulating ncRNAs, particularly miRNAs, are dysregulated after splenectomy.
- These ncRNAs may play a role in the immune alterations and complications following splenectomy.
- The findings highlight the potential of ncRNAs as biomarkers or therapeutic targets in post-splenectomy care.
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