MicroRNA-141 regulates the tumour suppressor DLC1 in colorectal cancer

Neoplasma
|August 18, 2015
PubMed

Insights

MicroRNA-141 (miR-141) promotes colorectal cancer (CRC) growth and invasion by targeting the tumor suppressor DLC1. This study reveals miR-141 as a potential oncogene in CRC, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Previous research identified DLC1 as a tumor suppressor in colorectal cancer (CRC).
  • The role of microRNA (miRNA) regulation in DLC1 function within CRC remained unclear.

Purpose of the Study:

  • To investigate if DLC1 is a target of miRNA regulation in CRC.
  • To evaluate the functional role of the miR-141/DLC1 axis in colorectal cancer progression.

Main Methods:

  • Bioinformatic analysis and literature review identified miR-141.
  • In vitro studies involved transfecting Lovo cells with miR-141 mimic/inhibitor.
  • Cell growth, cell cycle, invasion, and gene expression were assessed using MTT assays, flow cytometry, transwell assays, luciferase reporter assays, and Western blots.
  • In vivo tumor models and analysis of clinical CRC samples were conducted.

Main Results:

  • DLC1 was confirmed as a direct target of miR-141 in CRC.
  • miR-141 was significantly upregulated, and DLC1 downregulated in CRC tissues, showing a negative correlation.
  • miR-141 overexpression enhanced CRC cell proliferation, cell cycle progression, and invasion in vitro and in vivo.
  • Restoring DLC1 expression in miR-141-overexpressing cells suppressed tumor growth and invasion.

Conclusions:

  • miR-141 is upregulated in colorectal cancer and functions as an oncogene.
  • The oncogenic role of miR-141 in CRC is mediated through the suppression of its target, DLC1.
  • The miR-141/DLC1 pathway represents a potential therapeutic target for colorectal cancer treatment.

Related Concept Videos

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...
4.3K
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...
24.7K
MicroRNAs01:22

MicroRNAs

12.1K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
10.2K
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...
5.4K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.6K