Related Experiment Video

Updated: Aug 26, 2025

Efficient Gene Knockdown in the Liver via Intrasplenic Injection of Adeno-Associated Virus Serotype 8 (AAV8)-Delivered Small Hairpin RNA
04:29

Efficient Gene Knockdown in the Liver via Intrasplenic Injection of Adeno-Associated Virus Serotype 8 (AAV8)-Delivered Small Hairpin RNA

Published on: November 1, 2024

464

Melatonin inhibits HCC progression through regulating the alternative splicing of NEMO

Lu Bai1, Siwen Sun2, Wenmei Su3

  • 1Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.

Frontiers in Pharmacology
|October 13, 2022
PubMed

Insights

Melatonin inhibits hepatocellular carcinoma (HCC) growth by altering gene expression and RNA splicing. This neuroendocrine hormone regulates key cancer pathways, offering a new therapeutic approach for HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Hepatocellular carcinoma (HCC) presents limited therapeutic options.
  • Melatonin, a neuroendocrine hormone, shows anti-cancer effects in various cancers, including HCC.
  • The role of melatonin in regulating RNA alternative splicing in HCC is not well understood.

Purpose of the Study:

  • To investigate the anti-cancer effects of melatonin on HCC.
  • To elucidate the mechanisms by which melatonin suppresses HCC growth, focusing on RNA alternative splicing.
  • To explore the role of melatonin receptor MT1 in mediating these effects.

Main Methods:

  • Investigated melatonin's effect on HCC cell growth (HepG2 cells).
  • Analyzed transcriptional alterations and RNA alternative splicing events induced by melatonin.
  • Examined the involvement of melatonin receptor MT1 and its downstream targets, including IKBKG (NEMO).

Main Results:

  • Melatonin inhibited HCC cell growth.
  • Melatonin induced significant transcriptional changes in genes related to DNA replication, repair, and extracellular matrix functions.
  • Melatonin regulated cancer-related alternative splicing events, impacting cell cycle and kinase activity, partially via MT1.
  • Melatonin increased the production of a long isoform of NEMO (NEMO-L) with exon 5 inclusion, inhibiting HepG2 cell growth.

Conclusions:

  • Melatonin suppresses HCC growth through novel mechanisms involving the regulation of RNA alternative splicing.
  • Melatonin's effects are mediated partly by the MT1 receptor and impact key cellular processes.
  • This study provides a new perspective on melatonin as a potential therapeutic agent for HCC by targeting RNA splicing.
Keywords:
HCCMT1NEMOalternative splicingmelatonin

More Related Videos

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines08:50

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 2025

520
In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells11:56

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

Published on: September 28, 2017

9.9K

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...
3.1K
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...
4.6K
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...
7.4K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.3K
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...
6.4K
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...
4.9K