MiR-208a-3p functions as an oncogene in colorectal cancer by targeting PDCD4

Henglan Wu1, Lele Xu2, Yaou Chen2

  • 1Department of Nephrology, First Affiliated Hospital of Jiaxing University, Jiaxing,China.

Bioscience Reports
|March 28, 2019
PubMed

Insights

MicroRNAs (miRNAs) like miR-208a-3p promote colorectal cancer (CRC) growth by targeting the tumor suppressor PDCD4. Inhibiting miR-208a-3p may offer a new therapeutic strategy for CRC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are crucial regulators in human cancer development, including colorectal cancer (CRC).
  • The specific roles and mechanisms of many miRNAs in CRC progression require further elucidation.
  • Understanding miRNA functions is vital for identifying novel diagnostic and therapeutic targets in CRC.

Purpose of the Study:

  • To investigate the biological function and molecular mechanism of miR-208a-3p in colorectal cancer.
  • To identify potential downstream targets of miR-208a-3p involved in CRC pathogenesis.
  • To evaluate miR-208a-3p as a potential biomarker for CRC diagnosis and therapy.

Main Methods:

  • Microarray analysis to identify differentially expressed miRNAs in CRC tissues.
  • Functional assays (proliferation, invasion, migration, apoptosis) to assess miR-208a-3p's role in CRC cells.
  • Target validation using luciferase reporter assays and Western blotting to confirm PDCD4 as a direct target.

Main Results:

  • miR-208a-3p was significantly upregulated in CRC tissues and associated with advanced TNM stage and distant metastasis.
  • Inhibition of miR-208a-3p suppressed CRC cell proliferation, invasion, and migration, while inducing apoptosis.
  • miR-208a-3p directly targets and downregulates the tumor suppressor programmed cell death protein 4 (PDCD4).
  • PDCD4 overexpression inhibited CRC cell growth, and its silencing reversed the effects of miR-208a-3p inhibition.

Conclusions:

  • miR-208a-3p acts as an oncogene in colorectal cancer by targeting PDCD4.
  • The miR-208a-3p/PDCD4 axis plays a critical role in promoting CRC progression.
  • miR-208a-3p represents a promising diagnostic and therapeutic biomarker for colorectal cancer.

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
11.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.7K
Functional Groups02:45

Functional Groups

Functional groups are a group of atoms with characteristic properties, which when linked to the carbon skeleton of a molecule, alter the properties of that molecule. For example, the presence of certain functional groups on a molecule will make them hydrophilic, whereas others will make them hydrophobic. These functional groups are an indispensable part of organic chemistry and important components of biological molecules, such as carbohydrates, proteins, lipids, and nucleic acids. Each...
88.2K
Functional Groups02:45

Functional Groups

24.3K
Cancer02:18

Cancer

Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
53.9K
What is Cancer?02:12

What is Cancer?

Cells and tissues must meticulously coordinate their activities for the normal functioning of the human body. Therefore, they exhibit socially responsible behavior - resting, growing, dividing, differentiating, or dying - for the organism’s benefit. Cancer arises when cells divide uncontrollably and invade other tissues or organs.
Although people have known about cancer for centuries, it was only in 1761 that Giovanni Morgagni of Padua performed a detailed autopsy of...
14.1K