The LINC00152/miR-145-5p/KLF4 ceRNA axis shows preliminary diagnostic and prognostic potential for aortic dissection, and drives AD development by regulating vascular inflammation and extracellular matrix degradation.
Key Findings
Results
LINC00152 and KLF4 were upregulated while miR-145-5p was downregulated in aortic dissection patients compared to healthy controls.
105 aortic dissection (AD) patients and 55 healthy controls were enrolled in the study.
Expression levels were measured by quantitative reverse transcription PCR (qRT-PCR).
The differential expression pattern of all three molecules was consistent with a ceRNA regulatory axis.
These expression differences formed the basis for downstream diagnostic and prognostic analyses.
Results
The combined three-molecule panel demonstrated good diagnostic efficacy for aortic dissection.
The combined area under the ROC curve (AUC) for LINC00152, miR-145-5p, and KLF4 together was 0.9087.
ROC curve analysis was used to assess diagnostic value for each molecule individually and in combination.
The combined AUC of 0.9087 indicates strong discriminatory ability between AD patients and healthy controls.
Individual molecules were also assessed for diagnostic efficacy, with the combination outperforming individual biomarkers.
Results
LINC00152, KLF4, and their joint risk signature were identified as independent prognostic factors for adverse outcomes in aortic dissection patients.
Cox regression analysis was used to assess the prognostic value of the three molecules.
Both LINC00152 and KLF4 individually qualified as independent prognostic factors for adverse outcomes.
A joint risk signature combining LINC00152 and KLF4 also independently predicted adverse outcomes.
miR-145-5p's independent prognostic role is implied through the axis but specific Cox results for it alone are not separately stated in the abstract.
Results
LINC00152 mechanistically sponges miR-145-5p to upregulate KLF4, thereby promoting pro-inflammatory factors and matrix metalloproteinases in human aortic smooth muscle cells (HASMCs).
The ceRNA axis was validated using dual-luciferase reporter assays and rescue experiments.
Experiments were conducted in angiotensin II (Ang II)-induced HASMCs as an in vitro model of AD.
Pro-inflammatory factors upregulated through this axis included TNF-α and IL-1β.
Matrix metalloproteinases upregulated through this axis included MMP-2 and MMP-9, which are implicated in extracellular matrix degradation.
The mechanism involves LINC00152 acting as a competitive endogenous RNA (ceRNA) that sequesters miR-145-5p, relieving its suppression of KLF4.
Results
The LINC00152/miR-145-5p/KLF4 axis drives aortic dissection development by regulating vascular inflammation and extracellular matrix degradation.
Upregulation of TNF-α and IL-1β represents the pro-inflammatory component of the axis's pathological effect.
Upregulation of MMP-2 and MMP-9 represents the extracellular matrix degradation component.
Both processes are known contributors to aortic wall weakening and dissection progression.
The authors propose this axis as a candidate molecular target for subsequent translational research.
What This Means
Aortic dissection is a life-threatening emergency where the inner layer of the body's main artery tears, and early detection and risk assessment remain challenging. This study examined a molecular signaling chain—involving a long non-coding RNA called LINC00152, a small RNA called miR-145-5p, and a protein called KLF4—in 105 aortic dissection patients and 55 healthy individuals. The researchers found that LINC00152 and KLF4 were abnormally elevated in patients, while miR-145-5p was reduced, and that measuring all three together could distinguish patients from healthy individuals with high accuracy (combined AUC of ~0.91, where 1.0 would be perfect). Elevated LINC00152 and KLF4 levels also predicted worse outcomes in patients, suggesting they may have value not just for diagnosis but for identifying who is at higher risk.
In laboratory experiments using human aortic smooth muscle cells treated with a stress hormone (angiotensin II) to mimic disease conditions, the researchers confirmed how this molecular chain works: LINC00152 acts like a 'sponge' that soaks up miR-145-5p, preventing it from doing its normal job of keeping KLF4 in check. When KLF4 goes unchecked, it ramps up inflammation (via TNF-α and IL-1β) and activates enzymes (MMP-2 and MMP-9) that break down the structural scaffolding of the artery wall—both of which can worsen aortic dissection.
This research suggests that the LINC00152/miR-145-5p/KLF4 signaling axis could serve as a set of blood-based biomarkers to help diagnose aortic dissection and assess patient prognosis. It also points to this pathway as a potential target for future therapies aimed at reducing arterial inflammation and structural damage. However, the study is preliminary, involves a relatively small patient group, and further validation in larger and more diverse populations is needed before any clinical application could be considered.
Guan X, Li J. (2026). LINC00152/miR-145-5p/KLF4 ceRNA Axis: Diagnostic and Prognostic Value in Aortic Dissection.. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. https://doi.org/10.1111/apm.70248