Uncovering the new landscape of leukoaraiosis through the circular RNA-miRNA-mRNA axis

Canmin Zhu1, Chang Chang1, Qiangjian Jin1

  • 1Department of Neurology, The First People's Hospital of Jiangxia District, Wuhan, Hubei, China.

Frontiers in Neurology
|November 20, 2025
PubMed
Abstract

Insights

Circular RNA hsa_circ_0018401 is elevated in white matter injury (WMI) and regulates the miR-145-5p/AIFM1 axis. This finding offers a potential biomarker and therapeutic target for WMI.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • White matter disease, characterized by oligodendrocyte progenitor cell loss, is linked to poor outcomes in leukoaraiosis (LA) patients.
  • The regulatory roles of circ-RNA/miRNA/mRNA in brain disorders are known, but their specific mechanisms in white matter injury (WMI) are not well understood.

Purpose of the Study:

  • To investigate the involvement of the hsa_circ_0018401/miR-145-5p/AIFM1 axis in white matter injury.
  • To explore the potential of circ-0018401 as a biomarker and therapeutic target for WMI.

Main Methods:

  • Quantitative real-time polymerase chain reaction (qRT-PCR) and bioinformatics tools were used to analyze whole blood samples from LA patients.
  • Luciferase gene assays and qRT-PCR confirmed the interaction between circ-0018401, miR-145-5p, and AIFM1 in primary oligodendrocyte progenitor cells (OPCs) and HEK-293T cells.
  • Western blotting analyzed AIFM1 expression in OPCs overexpressing miR-145-5p.

Main Results:

  • Elevated circ-0018401 levels were detected in the whole blood of WMI patients.
  • Overexpression of circ-0018401 led to decreased miR-145-5p levels in OPCs, with verified binding between circ-0018401 and miR-145-5p.
  • The apoptotic gene AIFM1 was identified as a downstream target of miR-145-5p.

Conclusions:

  • Hsa_circ_0018401 functions as a key regulator of the miR-145-5p/AIFM1 axis in white matter injury.
  • This axis represents a promising avenue for developing novel therapeutic strategies for WMI.

Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
9.7K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

3.4K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.7K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
23.8K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.6K
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
7.2K