CircLZIC regulates ox-LDL-induced HUVEC cell proliferation and apoptosis via Micro-330-5p/NOTCH2 axis in

Xingping Men1, Aizhen Hu1, Tingting Xu1

  • 1Department of Cardiology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.

Insights

Circular RNA LZIC (circLZIC) promotes atherosclerosis by inhibiting MicroRNA-330-5p, leading to increased NOTCH2 expression and HUVEC cell proliferation, while suppressing apoptosis. This highlights circLZIC as a key regulator in atherosclerosis development.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Epigenetics

Background:

  • Atherosclerosis (AS) is a leading cause of cardiovascular disease, driven by chronic inflammation.
  • Circular RNAs (circRNAs) are emerging as critical epigenetic regulators of vascular inflammation and AS progression.
  • Understanding circRNAs that modulate ox-LDL levels is crucial for deciphering AS pathology.

Purpose of the Study:

  • To investigate the role of circLZIC in regulating atherosclerosis (AS) through the MicroRNA-330-5p/NOTCH2 axis.
  • To elucidate the molecular mechanisms by which circLZIC influences human umbilical vein endothelial cell (HUVEC) behavior in the context of AS.

Main Methods:

  • Analysis of circLZIC, MicroRNA-330-5p, and NOTCH2 expression in human AS samples.
  • Cell proliferation (CCK-8) and apoptosis (flow cytometry) assays in HUVECs.
  • RNA interference, dual-luciferase reporter assays, and RIP-qRT-PCR to confirm regulatory interactions.

Main Results:

  • CircLZIC and NOTCH2 were highly expressed in AS samples, while MicroRNA-330-5p was locally expressed.
  • CircLZIC promoted HUVEC proliferation and inhibited apoptosis; its knockdown increased MicroRNA-330-5p, promoted apoptosis, and inhibited NOTCH2.
  • MicroRNA-330-5p targeted NOTCH2, and its overexpression reduced NOTCH2 expression, inhibited apoptosis, and decreased cell activity.

Conclusions:

  • CircLZIC promotes HUVEC proliferation and inhibits apoptosis via the MicroRNA-330-5p/NOTCH2 pathway.
  • CircLZIC plays a significant role in the development of atherosclerosis.
  • The circLZIC/MicroRNA-330-5p/NOTCH2 axis represents a potential therapeutic target for AS.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K
Inflammation01:38

Inflammation

Overview
53.4K
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.2K