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miRNA‑29a inhibits the proliferation of HUVECs by regulating the ITGB1/β‑catenin/c‑Myc pathway

  • Authors:
    • Qi Sun
    • Wenting Chen
    • Shan Zhang
    • Xinni Zhong
    • Yafen Wu
    • Yingying Qian
    • Lei Zhu
    • Ting Zhang
    • Wei Li
  • View Affiliations / Copyright

    Affiliations: Department of Dermatology, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 115
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    Published online on: February 12, 2026
       https://doi.org/10.3892/mmr.2026.13825
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Abstract

Infantile hemangioma (IH) is a type of benign vascular tumor observed in younger patients. Previously, 216 differentially expressed microRNAs (miRs/miRNAs) associated with IH have been identified. In addition, common hub genes and miRNAs related to proteoglycan signaling pathways in angiogenesis and cancer have been identified, including c‑Myc, integrin β1 (ITGB1), Bcl2 and miR‑29a. Therefore, the present study aimed to explore the pathogenesis of IH from the perspective of previously identified miRNA gene network and protein‑protein interactions. Gene and protein levels in human umbilical vein endothelial cells (HUVECs) were analyzed using reverse transcription‑quantitative PCR and western blot (WB) analysis. Cell viability was assessed using a Cell Counting Kit‑8 assay, and the potential association between miR‑29a with ITGB1 was validated using a dual‑luciferase reporter assay. The inhibition of ITGB1 suppressed the β‑catenin/c‑Myc pathway in HUVECs. In addition, transfection with small interfering RNAs (siRNAs) targeting ITGB1 decreased the viability of HUVECs. Furthermore, siRNAs targeting mucin 1 and β‑N‑acetylglucosaminidase significantly inhibited the c‑Myc pathway in HUVECs. The results of WB and dual‑luciferase reporter assays demonstrated that miR‑29a regulated the β‑catenin/c‑Myc pathway and the viability of HUVECs in HUVECs by directly binding to ITGB1. Therefore, miR‑29a may serve as a potential therapeutic target for IH.
View Figures

Figure 1

Inhibition of ITGB1 downregulates the
β-catenin/c-Myc pathway in HUVECs. (A) ITGB1 gene expression after
HUVECs were transfected with 20 nM ITGB1 siRNA1, siRNA2 or siRNA
negative control for 6 h, and cultured for another 48 h. The gene
expressions of (B) ITGB1-DT, (C) EZH2 and (D) c-Myc were assessed
using reverse transcription-quantitative PCR following transfection
with ITGB1 siRNA. (E) The protein expression levels of ITGB1, TCF1,
EZH2, c-Myc, p-GSK3β, GSK3β, p-β-catenin and β-catenin were
evaluated using western blotting following transfection with ITGB1
siRNA. (F) Semi-quantification of western blotting results. p-GSK3β
and p-β-catenin were normalized to the levels of total GSK3β or
β-catenin, respectively. (G) Cell viability was analyzed using a
Cell Counting Kit-8 assay. n=3; *P<0.05 and **P<0.01 compared
with siRNA control group. HUVECs, human umbilical vein endothelial
cells; ITGB1, integrin β1; ITGB1-DT, integrin subunit β1 divergent
transcript; EZH2, histone-lysine N-methyltransferase EZH2; siRNA,
small interfering RNA; TCF1, T-cell factor 1; p-,
phosphorylated.

Figure 2

Inhibition of MUC1 downregulates the
c-Myc pathway in HUVECs. HUVECs were transfected with 20 nM MUC1
siRNA1, siRNA2 or siRNA negative control for 6 h and cultured for
another 48 h. The gene expressions of (A) MUC1 and (B) c-Myc were
assessed using reverse transcription-quantitative PCR. (C) Cell
viability was analyzed using a Cell Counting Kit-8 assay. n=3;
**P<0.01 compared with siRNA control group. HUVECs, human
umbilical vein endothelial cells; siRNA, small interfering RNA;
MUC1, mucin 1.

Figure 3

Inhibition of OGT downregulates the
c-Myc pathway in HUVECs. HUVECs were transfected with 20 nM OGT
siRNA1, siRNA2 or siRNA negative control for 6 h and cultured for
another 48 h. The gene expressions of (A) OGT, (B) OGA and (C)
c-Myc were detected using reverse transcription-quantitative PCR.
(D) OGT, OGA and c-Myc protein expression levels were assessed
using western blotting and (E) semi-quantified. (F) Cell viability
was analyzed via Cell Counting Kit-8 assay. n=3; **P<0.01
compared with siRNA control group. HUVECs, human umbilical vein
endothelial cells; OGT, O-linked N-acetylglucosamine transferase
110 kDa subunit; OGA, β-N-acetylglucosaminidase; siRNA, small
interfering RNA.

Figure 4

miR-29a inhibits ITGB1 gene
expression. HUVECs were transfected with 20 µg/ml miR-29a mimic,
mimic NC, miR-29a inhibitor or inhibitor control for 6 h and
cultured for another 48 h. The gene expression levels of (A)
miR-29a (**P<0.01 compared with miRNA-NC or inhibitor-ctrl group
respectively), (B) ITGB1, (C) ITGB1-DT, (D) MUC1 and (E) c-Myc were
assessed using reverse transcription-quantitative PCR. n=3;
**P<0.01 compared with the miRNA-NC group. miR/miRNA, microRNA;
ITGB1, integrin β1; HUVECs, human umbilical vein endothelial cells;
NC, negative control; miRNA-NC, miR-29a mimic negative control;
ITGB1-DT, integrin subunit β1 divergent transcript; MUC1, mucin 1;
inhibitor-ctrl, miR-29a inhibitor negative control.

Figure 5

miR-29a downregulates the
β-catenin/c-Myc pathway in HUVECs by targeting ITGB1. HUVECs were
transfected with 20 µg/ml miR-29a mimics, miR-29a inhibitor or
negative control for 6 h and cultured for another 48 h. (A) The
protein expression levels of OGT, OGA, ITGB1, TCF1, c-Myc, p-GSK3β,
GSK3β, p-β-catenin and β-catenin were assessed using western
blotting and (B) semi-quantified. p-GSK3β and p-β-catenin were
normalized to the levels of total GSK3β or β-catenin, respectively.
(C) Cell viability was analyzed using a Cell Counting Kit-8 assay.
The interaction between miR-29a and ITGB1 was validated using (D)
TargetScan and (E) via dual-luciferase reporter assay (**P<0.01
compared with miR NC + ITGB1 WT group). (F) A schematic figure
illustrating the interactions among miR-29a, ITGB1 and the c-Myc
pathway. n=3; *P<0.05 and **P<0.01 compared with miRNA-NC
group. miR/miRNA, microRNA; HUVECs, human umbilical vein
endothelial cells; ITGB1, integrin β1; OGT, O-linked
N-acetylglucosamine transferase 110 kDa subunit; OGA,
β-N-acetylglucosaminidase; TCF1, T-cell factor 1; p-
phosphorylated; hsa-miR, human microRNA; NC, negative control; WT,
wild-type; Mut, mutant.
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Copy and paste a formatted citation
Spandidos Publications style
Sun Q, Chen W, Zhang S, Zhong X, Wu Y, Qian Y, Zhu L, Zhang T and Li W: miRNA‑29a inhibits the proliferation of HUVECs by regulating the ITGB1/&beta;‑catenin/c‑Myc pathway. Mol Med Rep 33: 115, 2026.
APA
Sun, Q., Chen, W., Zhang, S., Zhong, X., Wu, Y., Qian, Y. ... Li, W. (2026). miRNA‑29a inhibits the proliferation of HUVECs by regulating the ITGB1/&beta;‑catenin/c‑Myc pathway. Molecular Medicine Reports, 33, 115. https://doi.org/10.3892/mmr.2026.13825
MLA
Sun, Q., Chen, W., Zhang, S., Zhong, X., Wu, Y., Qian, Y., Zhu, L., Zhang, T., Li, W."miRNA‑29a inhibits the proliferation of HUVECs by regulating the ITGB1/&beta;‑catenin/c‑Myc pathway". Molecular Medicine Reports 33.4 (2026): 115.
Chicago
Sun, Q., Chen, W., Zhang, S., Zhong, X., Wu, Y., Qian, Y., Zhu, L., Zhang, T., Li, W."miRNA‑29a inhibits the proliferation of HUVECs by regulating the ITGB1/&beta;‑catenin/c‑Myc pathway". Molecular Medicine Reports 33, no. 4 (2026): 115. https://doi.org/10.3892/mmr.2026.13825
Copy and paste a formatted citation
x
Spandidos Publications style
Sun Q, Chen W, Zhang S, Zhong X, Wu Y, Qian Y, Zhu L, Zhang T and Li W: miRNA‑29a inhibits the proliferation of HUVECs by regulating the ITGB1/&beta;‑catenin/c‑Myc pathway. Mol Med Rep 33: 115, 2026.
APA
Sun, Q., Chen, W., Zhang, S., Zhong, X., Wu, Y., Qian, Y. ... Li, W. (2026). miRNA‑29a inhibits the proliferation of HUVECs by regulating the ITGB1/&beta;‑catenin/c‑Myc pathway. Molecular Medicine Reports, 33, 115. https://doi.org/10.3892/mmr.2026.13825
MLA
Sun, Q., Chen, W., Zhang, S., Zhong, X., Wu, Y., Qian, Y., Zhu, L., Zhang, T., Li, W."miRNA‑29a inhibits the proliferation of HUVECs by regulating the ITGB1/&beta;‑catenin/c‑Myc pathway". Molecular Medicine Reports 33.4 (2026): 115.
Chicago
Sun, Q., Chen, W., Zhang, S., Zhong, X., Wu, Y., Qian, Y., Zhu, L., Zhang, T., Li, W."miRNA‑29a inhibits the proliferation of HUVECs by regulating the ITGB1/&beta;‑catenin/c‑Myc pathway". Molecular Medicine Reports 33, no. 4 (2026): 115. https://doi.org/10.3892/mmr.2026.13825
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