MicroRNA-448 inhibits the regeneration of spinal cord injury through PI3K/AKT/Bcl-2 axis

C-L Lv1, T Zhang, T-Z Yan

  • 1Department of Spine Surgery, Jining No. 1 People's Hospital, Jining, China. gaokaijizhuwai@163.com.

Abstract

Insights

MicroRNA-448 increases after spinal cord injury (SCI) and aids motor nerve regeneration by regulating the PI3K/AKT/Bcl-2 pathway. Inhibiting microRNA-448 improves grip strength and motor neuron recovery in SCI mice.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Regenerative Medicine

Background:

  • Spinal cord injury (SCI) leads to significant motor function deficits.
  • Understanding molecular mechanisms driving SCI recovery is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of microRNA-448 in spinal cord injury recovery.
  • To explore the underlying molecular mechanisms involving the PI3K/AKT/Bcl-2 pathway.

Main Methods:

  • Established a mouse model of spinal cord injury.
  • Utilized microarray, bioinformatics, and Dual-Luciferase reporter gene assays.
  • Administered microRNA-448 mimics/inhibitors and Bcl-2 siRNA, followed by qRT-PCR and Western blot analysis.

Main Results:

  • MicroRNA-448 expression increased post-SCI, inversely correlating with Bcl-2 levels.
  • MicroRNA-448 directly targets and downregulates Bcl-2.
  • Inhibition of microRNA-448 enhanced motor neuron regeneration and grip strength, mediated via the PI3K/AKT/Bcl-2 pathway.

Conclusions:

  • MicroRNA-448 upregulation post-SCI plays a role in spinal motor nerve regeneration.
  • The PI3K/AKT/Bcl-2 signaling axis is a key mechanism regulated by microRNA-448 in SCI recovery.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.4K
Spinal Cord01:26

Spinal Cord

The spinal cord, a critical component of the central nervous system, extends from the base of the brainstem to the lumbar region of the vertebral column. It is essential for maintaining physical stability and facilitating communication between the brain and peripheral parts of the body.
1.6K
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...
24.1K
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...
3.9K
The Spinal Cord01:54

The Spinal Cord

The spinal cord is the body’s major nerve tract of the central nervous system, communicating afferent sensory information from the periphery to the brain and efferent motor information from the brain to the body. The human spinal cord extends from the hole at the base of the skull, or foramen magnum, to the level of the first or second lumbar vertebra.
31.6K
Spinal Cord: Information Processing01:10

Spinal Cord: Information Processing

The spinal cord is an integral hub for motor and sensory information that enables the brain to communicate with the peripheral nervous system (PNS). This communication consists of relaying sensory data and transmission of motor commands.
Sensory Information Processing
Sensory information processing begins at the sensory receptors located in the skin and other tissues, which detect somatic sensory stimuli such as touch, temperature, or pain. These receptors function as catalysts, initiating...
3.3K