MicroRNA-106a-5p Inhibited C2C12 Myogenesis via Targeting PIK3R1 and Modulating the PI3K/AKT Signaling

Xiao Li1, Youbo Zhu2, Huifang Zhang3

  • 1Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A and F University, Yangling 712100, China. nicelixiao@nwsuaf.edu.cn.

Genes
|July 14, 2018
PubMed

Insights

MicroRNA-106a-5p inhibits muscle cell differentiation and promotes atrophy by targeting PIK3R1, impacting the PI3K/AKT signaling pathway. This microRNA is elevated in aged and dexamethasone-treated muscles.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression.
  • The miR-17 family plays diverse roles in mammalian tissues.
  • Myogenic differentiation is crucial for muscle development and repair.

Purpose of the Study:

  • To investigate the function of miR-106a-5p in C2C12 cell myogenic differentiation.
  • To explore the role of miR-106a-5p in muscle aging and atrophy.
  • To elucidate the molecular mechanism underlying miR-106a-5p's effects on muscle cells.

Main Methods:

  • Quantitative real-time PCR to measure miRNA and gene expression.
  • Cell culture of C2C12 myoblasts and myotubes.
  • Overexpression and inhibition of miR-106a-5p.
  • Western blotting to assess protein phosphorylation.
  • Luciferase reporter assay to confirm direct binding.

Main Results:

  • miR-106a-5p expression decreased during myogenic differentiation but increased in aged and dexamethasone-treated muscles.
  • Forced miR-106a-5p expression inhibited differentiation, reduced myogenic marker expression, and decreased phosphorylated AKT.
  • miR-106a-5p overexpression in myotubes led to reduced diameter, increased atrophy gene expression, and decreased PI3K/AKT activity.
  • miR-106a-5p directly targets PIK3R1 3'-UTR, repressing PI3K/AKT signaling.

Conclusions:

  • miR-106a-5p acts as a negative regulator of myogenic differentiation.
  • Elevated miR-106a-5p contributes to muscle aging and atrophy by inhibiting the PI3K/AKT pathway.
  • Targeting miR-106a-5p may offer therapeutic potential for muscle-related disorders.

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...
5.6K
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...
24.3K
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...
4.0K
Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.2K
What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
131.0K
Endocrine Signaling01:45

Endocrine Signaling

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
68.2K