UVB drives different stages of epigenome alterations during progression of skin cancer

Yuqing Yang1, Renyi Wu2, Davit Sargsyan2

  • 1Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA; Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.

Cancer Letters
|February 17, 2019
PubMed

Insights

UVB irradiation alters DNA methylation in mouse skin, impacting cancer-related pathways and identifying novel genes. These findings offer potential targets for non-melanoma skin cancer prevention and treatment.

Area of Science:

  • Oncology
  • Epigenetics
  • Dermatology

Background:

  • Ultraviolet B (UVB) irradiation causes DNA damage and is linked to non-melanoma skin cancers (NMSCs).
  • While genetic mutations are known drivers, epigenetic alterations (epi-mutations) in NMSC development remain less understood.
  • Understanding epigenetic changes is crucial for comprehensive NMSC research.

Purpose of the Study:

  • To investigate genome-wide DNA CpG methylation profiles in UVB-irradiated mouse skin at various stages of carcinogenesis.
  • To correlate DNA methylation changes with transcriptome alterations in UVB-induced NMSC.
  • To identify novel genes and pathways involved in skin cancer development.

Main Methods:

  • Utilized CpG Methyl-seq for genome-wide DNA methylation profiling.
  • Performed RNA-seq to analyze corresponding transcriptome alterations.
  • Employed Ingenuity Pathway Analysis (IPA) to identify cancer-related signaling pathways.

Main Results:

  • UVB irradiation progressively altered DNA methylation profiles in mouse epidermis over time.
  • IPA revealed significant alterations in cancer-related pathways, including PTEN, p53, Nrf2, and inflammatory signaling.
  • Identified novel differentially methylated genes (Enf2, Mgst2, Vegfa, Cdk4) implicated in skin carcinogenesis.

Conclusions:

  • UVB-induced NMSC involves dynamic changes in DNA methylation and gene expression.
  • The study provides novel insights into the epigenetic landscape of skin carcinogenesis.
  • Identified potential therapeutic and preventative targets for NMSC at different disease stages.

Related Concept Videos

Skin Cancer01:30

Skin Cancer

Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
5.8K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.7K
Alterations in Respiration II01:30

Alterations in Respiration II

There are numerous types of normal and abnormal respiration. Based on ventilatory movements, breathing patterns are classified as regular, deep, or shallow. Examples include Biot's breathing, Cheyne-Stokes respiration, Kussmaul's breathing, hyperventilation, and hypoventilation. Each pattern is clinically significant and aids in evaluating patients.
In Biot's breathing, the respiratory rate and depth are irregular, alternating between periods of deep gasping and apnea. Common causes...
1.8K
Altered States of Awareness01:06

Altered States of Awareness

Altered states of consciousness represent significant deviations from one's normal mental state. These deviations can range from subtle changes in awareness to profound transformations in perception, thought processes, and sensory experiences. Altered states of consciousness can be triggered by various factors, including drug use, meditation, hypnosis, illness, or even intense fatigue.
The ingestion of substances like stimulants or hallucinogens leads to chemical alterations in the brain...
1.1K
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
2.8K
Alterations in Blood Pressure01:30

Alterations in Blood Pressure

Alterations in blood pressure, such as hypertension (high blood pressure) and hypotension (low blood pressure), significantly affect human health. Understanding these conditions' classifications, causes, and symptoms is essential for effective management and treatment.
Hypertension (High blood pressure)
Hypertension occurs when blood pressure readings consistently exceed the normal range. It is diagnosed when systolic blood pressure (the top number, indicating pressure while the heart...
2.1K