Tumor suppressor microRNA-27a in colorectal carcinogenesis and progression by targeting SGPP1 and Smad2

Yonghua Bao1, Zhiguo Chen2, Yongchen Guo3

  • 1Department of Immunology, Xinxiang Medical University, Xinxiang, China.

Plos One
|August 29, 2014
PubMed

Insights

MicroRNA-27a (miR-27a) is a tumor suppressor in colorectal cancer, with reduced levels linked to advanced stages. It targets SGPP1 and Smad2, inhibiting cancer cell growth and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant microRNA (miRNA) expression is implicated in colorectal cancer development.
  • The specific role and mechanisms of miRNA-27a (miR-27a) in colorectal carcinogenesis remain unclear.

Purpose of the Study:

  • To investigate the role of miR-27a in colorectal cancer.
  • To identify novel targets of miR-27a and elucidate its regulatory mechanisms in colorectal cancer progression.

Main Methods:

  • Quantitative analysis of miR-27a expression in colorectal cancer tissues and cell lines.
  • Bioinformatic analysis and experimental validation to identify miR-27a targets (SGPP1, Smad2).
  • In vitro functional assays (proliferation, apoptosis, migration) and in vivo studies in tumor-bearing mice.

Main Results:

  • miR-27a expression was significantly reduced in colorectal cancer tissues and cell lines, correlating with advanced clinical stages and metastasis.
  • SGPP1 and Smad2 were identified as direct targets of miR-27a, with their expression negatively correlated with miR-27a levels.
  • Increased miR-27a suppressed colon cancer cell proliferation, induced apoptosis (via cleaved caspase 3 upregulation), and reduced migration (via p-STAT3 downregulation).
  • In vivo, miR-27a inhibited tumor growth.

Conclusions:

  • miR-27a acts as a tumor suppressor in colorectal cancer.
  • SGPP1 and Smad2 are novel targets of miR-27a, contributing to its tumor-suppressive functions.
  • miR-27a, through targeting SGPP1, Smad2, and STAT3, regulates key cancer processes and holds potential as a biomarker and therapeutic target for colorectal cancer.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K
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...
20.9K
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...
3.0K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.9K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.2K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

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...
7.8K