MiR-449a regulates the cell migration and invasion of human non-small cell lung carcinoma by targeting ADAM10

Haining Meng1, Qiao Huang1, Xijin Zhang1

  • 1Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao 266021, People's Republic of China.

Insights

MicroRNA-449a acts as a tumor suppressor in non-small cell lung cancer (NSCLC). It inhibits cancer cell invasion and migration by targeting ADAM10, thus delaying tumor progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are crucial in tumorigenesis, but their precise role in non-small cell lung cancer (NSCLC) remains unclear.
  • miRNAs regulate gene expression and are implicated in various cellular processes relevant to cancer development.

Purpose of the Study:

  • To investigate the functional role of miRNA-449a in non-small cell lung cancer (NSCLC).
  • To elucidate the mechanism by which miRNA-449a affects NSCLC cell invasion and migration.

Main Methods:

  • Quantitative real-time PCR to assess miRNA-449a expression levels in NSCLC tissues and cell lines.
  • Transwell and Western Blot assays to evaluate cell invasion, migration, and protein expression.
  • Dual luciferase reporter assays to confirm the targeting relationship between miRNA-449a and ADAM10.

Main Results:

  • miRNA-449a was significantly down-regulated in NSCLC tissues and cell lines.
  • Upregulation of miRNA-449a suppressed NSCLC cell invasion and migration while decreasing ADAM10 expression.
  • Downregulation of miRNA-449a enhanced cell invasion and migration and increased ADAM10 expression.
  • miRNA-449a directly targets ADAM10, inhibiting epithelial-mesenchymal transition (EMT) progression.

Conclusions:

  • miRNA-449a functions as a tumor suppressor gene in NSCLC.
  • The tumor-suppressive activity of miRNA-449a is mediated through the inhibition of ADAM10 expression.
  • Targeting the miRNA-449a/ADAM10 axis may offer a therapeutic strategy for NSCLC.

Related Concept Videos

Cell Migration01:19

Cell Migration

Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
6.5K
Cell Migration01:09

Cell Migration

Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
18.7K
pH Regulation in Cells01:28

pH Regulation in Cells

pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
7.6K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.2K
Chemotaxis and Direction of Cell Migration01:21

Chemotaxis and Direction of Cell Migration

Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon...
4.4K
Role of Myosin in Cell Migration01:18

Role of Myosin in Cell Migration

Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II  is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
3.2K