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Interpretation of the molecular mechanism and therapeutic potential of microRNA‑155 in cardiovascular and cerebrovascular diseases (Review)

  • Authors:
    • Xitong Zhao
    • Pengqin Wang
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    Affiliations: First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110000, P.R. China, Department of Brain Disease Rehabilitation, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110000, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 10
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    Published online on: November 3, 2025
       https://doi.org/10.3892/ijmm.2025.5681
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Abstract

MicroRNA‑155 (miR‑155), a highly conserved non‑coding RNA, serves a pivotal role in the initiation and progression of cardiovascular and cerebrovascular diseases (CCVDs) through the modulation of target gene expression. miR‑155 contributes to the pathogenesis of conditions such as atherosclerosis, myocardial infarction, heart failure, hypertension and stroke, with mechanisms involving the regulation of endothelial function, inflammatory responses, oxidative stress, apoptosis and fibrosis. These findings suggest its potential as a biomarker. The present review provides a comprehensive overview of the biogenesis, regulation and biological functions of miR‑155, highlights its molecular mechanisms in CCVD progression, and examines current advances in therapeutic strategies targeting miR‑155, offering insights into the pathological mechanisms and precision treatment approaches for CCVDs.
View Figures

Figure 1

Generation process of miR-155. The
generation of miR-155 begins in the nucleus, where the primary
transcript (pri-miR-155) is processed by RNA pol II and the
double-stranded RNA-binding protein complex (Drosha/DGCR8) to
produce the miRNA precursor (pre-miR-155). During this process,
KSRP binds to the stem-loop structure of pri-miR-155 and recruits
the Drosha-DGCR8 complex to promote the processing of pri-miR-155
into pre-miR-155. In the cytoplasm, pre-miR-155 interacts with RNA
pol III and the transactivation response RNA-binding protein
complex (Dicer/TRBP) to form the mature miR-155. Ago2 binds to the
miR-155 double-stranded complex, forming the core of the RISC and
producing single-stranded DNA molecules. The two arms of the
pre-miRNA hairpin, known as miR-155-5p and miR-155-3p, generate
mature miRNAs with biological activity. Ago2, Argonaute protein 2;
DGCR8, DiGeorge syndrome critical region gene 8; Dicer, Dicer1
ribonuclease III; Drosha, Drosha ribonuclease III; KSRP, KH-type
splicing regulatory protein; miR/miRNA, microRNA; RISC, RNA-induced
silencing complex; RNA pol II, RNA polymerase II; TRBP,
trans-activation response element-binding protein.

Figure 2

Regulatory process of miR-155
expression. At the transcriptional level, the expression of miR-155
is regulated by NF-κB, AP-1 and STAT3. The maturation process,
involving cleavage and cytoplasmic transport from pri-miR-155 to
pre-miR-155, is modulated by factors such as LIN28, KSRP,
FLVCR1-AS1 and CircNr1h4. In pathological conditions, regulation by
MYC, TP35, ox-LDL, JAK/STAT, CTRP12 and Oprm1 has been observed.
AP-1, adaptor protein complex-1; CTRP12, C1q tumor necrosis factor
related protein 12; FLVCR1-AS1, feline leukemia virus subgroup C
receptor 1-antisense RNA 1; JAK, Janus kinase; KSRP, KH-type
splicing regulatory protein; LIN28, lineage protein 28; miR,
microRNA; Oprm1, opioid receptor Mu 1; ox-LDL, oxidized low-density
lipoprotein.

Figure 3

miR-155 participates in the
development of cardiovascular and cerebrovascular diseases through
interactions with multiple molecular pathways. ABCA1, ATP binding
cassette transporter A1; AGTR1, angiotensin II receptor subtype 1;
ANP, atrial natriuretic peptide; Ang II, angiotensin II; AT1R,
angiotensin II type I receptor; BAG5, Bcl-2-associated athanogene
5; BDNF, brain-derived neurotrophic factor; Cab39, calcium binding
protein 39; CREB, cAMP response element-binding protein; CYTOR,
cytoskeleton regulator RNA; cGMP, cyclic 3',5'-guanosine
monophosphate; DUSP14, dual specificity phosphatase 14; eNOS,
endothelial nitric oxide synthase; FOS, FOS proto-oncogene; HIF-1α,
hypoxia-inducible factor 1α; HO-1, heme oxygenase-1; JAK, Janus
kinase; LXRα, liver X receptor α; miR-155, microRNA-155; MafB,
V-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog B;
NPPA, natriuretic peptide A; MYD88, myeloid differentiation primary
response 88; NLRP3, NLR family pyrin domain containing 3; NO,
nitric oxide; PDCD4, programmed cell death 4; PKG1, protein kinase
G1; Rheb, ras homolog enriched in brain; SIRT1, sirtuin 1; sGCβ1,
soluble guanylate cyclase β1 subunit; SOCS1, suppressor of cytokine
signaling 1; TLR4, toll like receptor 4; ZIC3, Zic family member
3.

Figure 4

Molecular mechanisms of miR-155 in
the development of atherosclerosis. The left panel illustrates the
pathways through which miR-155 inhibits atherosclerosis. miR-155
suppresses PI3K, thereby inhibiting AKT and attenuating the
activation of mTOR. Simultaneously, it inhibits AT1R, reducing the
effects of Ang II and thereby inhibiting the progression of
atherosclerosis. Additionally, miR-155 inhibits MYD88, leading to
decreased NF-κB activity, and reduced production of TNF-α and
IL-6/8. miR-155 also suppresses LXRα, downregulating the expression
of ABCA1 and ABCG1, which impairs cholesterol reverse transport.
These combined effects collectively inhibit the onset and
development of atherosclerosis. The right panel depicts the
pathways through which miR-155 promotes the progression of
atherosclerosis. miR-155 inhibits sGCβ1, resulting in reduced NO
production. miR-155 also suppresses Bcl-6, leading to increased
NF-κB activity and subsequent activation of the NLRP3 inflammasome.
Furthermore, miR-155 inhibits SOCS1, thereby relieving its
suppression of p-STAT and PDCD4, which promotes the release of
pro-inflammatory cytokines such as TNF-α and IL-6, ultimately
exacerbating the progression of atherosclerosis. ABCA1, ATP binding
cassette transporter A1; ABCG1, ATP binding cassette transporter
G1; Ang II, angiotensin II; AT1R, angiotensin II type I receptor;
LXRα, liver X receptor α; miR-155, microRNA-155; MYD88, myeloid
differentiation primary response 88; NLRP3, NLR family pyrin domain
containing 3; NO, nitric oxide; p-, phosphorylated; PDCD4,
programmed cell death 4; sGCβ1, soluble guanylate cyclase β1
subunit; SOCS1, suppressor of cytokine signaling 1.

Figure 5

Molecular mechanisms of miR-155 in
the development of cardiac hypertrophy, myocardial infarction,
myocardial ischemia-reperfusion injury and heart failure. The left
panel corresponds to cardiac hypertrophy, where miR-155 suppresses
cardiac hypertrophy by inhibiting the protein expression of CYTOR,
thereby promoting the activation of IKKI protein, which
subsequently inhibits the protein activation of downstream AKT and
NF-κB. miR-155 also promotes the development of cardiac hypertrophy
by enhancing MAPK expression and inhibiting the expression of
FoxO3a. The middle left panel corresponds to myocardial infarction,
where miR-155 regulates SOCS1 and SIRT1. Low levels of miR-155 can
inhibit SOCS1 expression. NF-κB upregulated by the inhibition of
SOCS1 further regulates IL-1β, ultimately leading to myocardial
infarction. SIRT1 inhibits NLRP3 expression and thereby improves
myocardial infarction. Additionally, the middle right panel
corresponds to myocardial ischemia-reperfusion injury, where
miR-155 regulates SHP2, HIF-1α and JAK2. Elevated SHP expression
inhibits ERK1/2 activation, thereby ameliorating
ischemia-reperfusion injury. Concurrently, increased HIF-1α levels
promote MMP expression, which likewise attenuates ischemic damage.
Conversely, upregulation of JAK2 enhances STAT1 expression,
consequently exacerbating the progression of ischemia-reperfusion
injury. The right panel corresponds to heart failure, where miR-155
regulates HIF-1α and AKT, influencing Bax, Caspase-3 and CREB,
ultimately leading to heart failure. CREB, cAMP response
element-binding protein; CYTOR, cytoskeleton regulator RNA; HIF-1α,
hypoxia-inducible factor 1α; JAK2, Janus kinase 2; miR-155,
microRNA-155; NLRP3, NLR family pyrin domain containing 3; SHP2,
SHP, Src homology 2 domain-containing protein tyrosine phosphatase;
SIRT1, sirtuin 1; SOCS1, suppressor of cytokine signaling 1.

Figure 6

Molecular mechanisms of miR-155 in
cerebral ischemia-reperfusion and stroke development. The left
panel illustrates the regulatory pathways of miR-155 in cerebral
ischemia-reperfusion. miR-155 targets DUSP14, MafB, NRF2 and GATA3:
DUSP14 inhibits TXNIP, thereby influencing NLRP3; MafB suppresses
pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α; NRF2
promotes HO-1 expression; and GATA3 inhibits Caspase-3,
collectively participating in the regulation of cerebral
ischemia-reperfusion. The right panel shows the pathways through
which miR-155 mediates stroke progression. miR-155 regulates Wnt,
Rheb, JAK2 and TLR4, respectively activating the β-catenin,
mTOR-p-S6K, STAT3 and NF-κB pathways, thereby contributing to the
pathogenesis of stroke. DUSP14, dual specificity phosphatase 14;
GATA3, GATA binding protein 3; HO-1, heme oxygenase-1; JAK, Janus
kinase; MafB, V-Maf avian musculoaponeurotic fibrosarcoma oncogene
homolog B; miR-155, microRNA-155; NLRP3, NLR family pyrin domain
containing 3; NRF2, nuclear factor erythroid 2-related factor 2;
p-S6K, phosphorylated ribosomal protein S6 kinase; Rheb, Ras
homolog enriched in brain; TLR4, toll like receptor 4; TXNIP,
thioredoxin interacting protein.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao X and Wang P: Interpretation of the molecular mechanism and therapeutic potential of microRNA‑155 in cardiovascular and cerebrovascular diseases (Review). Int J Mol Med 57: 10, 2026.
APA
Zhao, X., & Wang, P. (2026). Interpretation of the molecular mechanism and therapeutic potential of microRNA‑155 in cardiovascular and cerebrovascular diseases (Review). International Journal of Molecular Medicine, 57, 10. https://doi.org/10.3892/ijmm.2025.5681
MLA
Zhao, X., Wang, P."Interpretation of the molecular mechanism and therapeutic potential of microRNA‑155 in cardiovascular and cerebrovascular diseases (Review)". International Journal of Molecular Medicine 57.1 (2026): 10.
Chicago
Zhao, X., Wang, P."Interpretation of the molecular mechanism and therapeutic potential of microRNA‑155 in cardiovascular and cerebrovascular diseases (Review)". International Journal of Molecular Medicine 57, no. 1 (2026): 10. https://doi.org/10.3892/ijmm.2025.5681
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao X and Wang P: Interpretation of the molecular mechanism and therapeutic potential of microRNA‑155 in cardiovascular and cerebrovascular diseases (Review). Int J Mol Med 57: 10, 2026.
APA
Zhao, X., & Wang, P. (2026). Interpretation of the molecular mechanism and therapeutic potential of microRNA‑155 in cardiovascular and cerebrovascular diseases (Review). International Journal of Molecular Medicine, 57, 10. https://doi.org/10.3892/ijmm.2025.5681
MLA
Zhao, X., Wang, P."Interpretation of the molecular mechanism and therapeutic potential of microRNA‑155 in cardiovascular and cerebrovascular diseases (Review)". International Journal of Molecular Medicine 57.1 (2026): 10.
Chicago
Zhao, X., Wang, P."Interpretation of the molecular mechanism and therapeutic potential of microRNA‑155 in cardiovascular and cerebrovascular diseases (Review)". International Journal of Molecular Medicine 57, no. 1 (2026): 10. https://doi.org/10.3892/ijmm.2025.5681
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