MiR-323a-3p suppressed the glycolysis of osteosarcoma via targeting LDHA

Hanwen Chen1, Shuming Gao2, Cai Cheng2

  • 1Department of First Orthopedics, Cangzhou Central Hospital, Cangzhou, 061000, Hebei, China. rmyy_med@sina.com.

Human Cell
|August 9, 2018
PubMed

Insights

MicroRNA-323a-3p is down-regulated in osteosarcoma (OS) and suppresses tumor growth by targeting lactate dehydrogenase A (LDHA), inhibiting cancer cell glycolysis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) play a critical role in cancer initiation and progression.
  • Dysregulation of specific miRNAs is implicated in various cancers, including osteosarcoma (OS).

Purpose of the Study:

  • To investigate the role of miR-323a-3p in osteosarcoma.
  • To identify the downstream targets and molecular mechanisms of miR-323a-3p in OS.

Main Methods:

  • Quantitative real-time PCR to assess miR-323a-3p and LDHA expression.
  • Cell viability, colony formation, and apoptosis assays to evaluate miR-323a-3p function.
  • Bioinformatics analysis to predict miR-323a-3p targets.
  • Western blot to confirm protein level changes.
  • Lactate production assays to assess glycolysis.

Main Results:

  • miR-323a-3p was significantly downregulated in OS tissues and cell lines.
  • Overexpression of miR-323a-3p inhibited OS cell viability, colony formation, and induced apoptosis.
  • Lactate dehydrogenase A (LDHA) was identified as a direct target of miR-323a-3p.
  • miR-323a-3p overexpression reduced LDHA mRNA and protein levels.
  • An inverse correlation was observed between miR-323a-3p and LDHA expression in OS tissues.
  • Overexpression of miR-323a-3p decreased lactate production in OS cells, indicating inhibition of glycolysis.

Conclusions:

  • miR-323a-3p acts as a tumor suppressor in osteosarcoma.
  • The miR-323a-3p/LDHA axis regulates osteosarcoma cell growth and glycolysis.
  • This study elucidates a novel molecular mechanism of miR-323a-3p in OS progression.

Related Concept Videos

What is Glycolysis?00:56

What is Glycolysis?

Overview
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
177.6K
Outcomes of Glycolysis01:13

Outcomes of Glycolysis

Nearly all the energy used by cells comes from the bonds that make up complex organic compounds. These organic compounds are broken down into simpler molecules, such as glucose. As a result, cells extract energy from glucose over many chemical reactions—a process called cellular respiration.
Cellular respiration can occur aerobically (with oxygen) or anaerobically (without oxygen). In the presence of oxygen, cellular respiration starts with glycolysis and continues with pyruvate...
107.3K
Energy-releasing Steps of Glycolysis01:28

Energy-releasing Steps of Glycolysis

Glycolysis is divided into two phases based on whether energy is utilized or released. While the first phase consumes ATP, the second phase produces energy in the form of ATP and NADH. The energy is released over a sequence of reactions that turns G3P into pyruvate. The energy-releasing phase—steps 6-10 of glycolysis—occurs twice, once for each of the two 3-carbon sugars produced during steps 1-5 of the first phase.
The first energy-releasing step—the 6th step of glycolysis...
146.9K
Energy-requiring Steps of Glycolysis01:20

Energy-requiring Steps of Glycolysis

Glucose is the source of nearly all energy used by organisms. The first step of converting glucose into usable energy is called glycolysis. Glycolysis occurs in the cytosol of the cell over two phases: an energy-requiring phase and an energy-releasing phase. Over the first three steps, glucose is converted into different forms and attached to two phosphate groups donated by two ATP molecules, resulting in an unstable sugar. In the next two stages, the unstable sugar splits into two sugar...
171.8K
Glycolysis01:23

Glycolysis

Glycolysis, the Embden-Meyerhof pathway, is a central metabolic pathway involved in glucose catabolism. It is highly conserved across most organisms, reflecting its fundamental role in cellular energy production. This process occurs in the cytoplasm and can function both in the presence and absence of oxygen, making it versatile for various organisms and environmental conditions.Stages of GlycolysisGlycolysis is a ten-step pathway that converts glucose into pyruvate, generating a net gain of...
1.7K
Glycolysis: Preparatory Phase01:21

Glycolysis: Preparatory Phase

In cellular metabolism (the complete breakdown of glucose to extract energy),  glycolysis is the first step. Glycolysis takes place in the cytoplasm of both prokaryotic and eukaryotic cells. Glucose enters heterotrophic cells in two ways. One method is through secondary active transport, where the transport takes place against the glucose concentration gradient. The other mechanism uses a group of integral proteins called GLUT proteins, also known as glucose transporter proteins. These...
17.1K