miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL

Lin Chen1, Haitao Guan1, Chunyan Gu1

  • 1Department of Gastroenterology and Clinical Laboratory, The Third People's Hospital of Nantong City, Jiangsu, 226006, China.

Insights

MicroRNA-383 (miR-383) is downregulated in hepatocellular carcinoma (HCC), correlating with poor prognosis. Restoring miR-383 suppresses HCC cell proliferation by targeting APRIL, suggesting a potential therapeutic strategy.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are small non-coding RNAs involved in gene regulation.
  • Dysregulation of miRNAs is common in human cancers, including hepatocellular carcinoma (HCC).
  • miRNAs play critical roles in cancer cell proliferation and progression.

Purpose of the Study:

  • To investigate the expression pattern of miR-383 in HCC.
  • To determine the correlation between miR-383 expression and HCC patient prognosis.
  • To elucidate the functional role of miR-383 in HCC cell proliferation and identify its target genes.

Main Methods:

  • Quantitative real-time PCR to assess miR-383 expression in HCC tissues and cell lines.
  • Kaplan-Meier analysis and Cox regression to evaluate prognostic significance.
  • In vitro functional assays (cell proliferation, cell cycle, apoptosis) to study miR-383 effects.
  • Luciferase reporter assay to identify miR-383 targets.
  • Western blot and rescue experiments to validate the miR-383-APRIL interaction.

Main Results:

  • miR-383 was significantly downregulated in HCC tissues and cell lines.
  • Lower miR-383 expression correlated with larger tumor size, advanced TNM stage, and poorer patient survival.
  • Ectopic miR-383 expression inhibited HCC cell proliferation, induced cell cycle arrest, and promoted apoptosis.
  • APRIL (a proliferation-inducing ligand) was identified as a direct target of miR-383.
  • APRIL overexpression rescued the anti-proliferative effect of miR-383 in HCC cells.

Conclusions:

  • miR-383 is a tumor suppressor in HCC, with its downregulation associated with tumor progression and poor prognosis.
  • miR-383 inhibits HCC cell proliferation, at least partially, by downregulating APRIL expression.
  • The miR-383-APRIL axis represents a potential therapeutic target for HCC treatment.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K
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
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
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.4K