miR-7-5p acts as a tumor suppressor in bladder cancer by regulating the hedgehog pathway factor Gli3

Jun Li1, Mingxing Qiu1, Yu An1

  • 1Department of Urology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, No. 32 West Second Section, First Ring Road, Chengdu, Sichuan, 610072, China.

Insights

MicroRNAs (miRNAs) regulate bladder cancer (BCa) progression. This study identifies miR-7-5p as a tumor suppressor that inhibits BCa by targeting Gli3, a key factor in the hedgehog pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Advanced bladder cancer (BCa) has a poor prognosis despite diagnostic and therapeutic advancements.
  • Understanding the molecular mechanisms driving BCa initiation and progression is crucial.
  • MicroRNAs (miRNAs) are known regulators of tumorigenesis by targeting messenger RNAs (mRNAs).

Purpose of the Study:

  • To investigate a novel miRNA-mRNA axis involved in bladder cancer progression.
  • To identify molecular targets and pathways implicated in BCa development.

Main Methods:

  • Microarray analysis to identify upregulated mRNAs in BCa tissues.
  • Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
  • Functional experiments (proliferation, migration, EMT assays) and rescue assays.
  • Kaplan-Meier survival analysis.

Main Results:

  • 182 mRNAs were upregulated in BCa tissues, associated with the hedgehog pathway.
  • Gli3, a hedgehog pathway factor, was upregulated and linked to unfavorable BCa prognosis.
  • Silencing Gli3 inhibited BCa cell proliferation, migration, and epithelial-mesenchymal transition (EMT).
  • miR-7-5p was identified as a direct targeting miRNA of Gli3 in BCa cells.

Conclusions:

  • miR-7-5p functions as a tumor suppressor in bladder cancer.
  • The miR-7-5p/Gli3 axis plays a significant role in regulating BCa progression.
  • Downregulation of Gli3 by miR-7-5p inhibits BCa cell growth and metastasis.

Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.1K
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...
9.8K
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...
6.1K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.6K
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
9.9K
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
8.2K