Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• Nitric oxide (NO) is recognized as a dual mediator in cancer, with its role dependent on dose, time, and location of generation.
• Epigenetic alterations significantly influence cancer development and progression.

Purpose of the Study:

• To review the epigenetic mechanisms regulating nitric oxide synthase (NOS) expression and NO production in cancer.
• To explore the impact of these mechanisms on cancer hallmarks and the tumor microenvironment.

Main Methods:

• Literature review focusing on epigenetic regulation of NOS and NO.
• Analysis of the roles of histone modifications, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) in NO production.
• Examination of the interplay between miRNAs, NO, and tumor microenvironment components.

Main Results:

• Epigenetic mechanisms, including histone modifications and ncRNAs (miRNAs and lncRNAs), directly or indirectly regulate NOS expression and NO production.
• Specific lncRNAs, such as HEIH and UCA1, promote tumor proliferation by inhibiting target miRNAs, thereby reversing NOS inhibition.
• The intricate connection between miRNAs and NO influences key cancer features, including the tumor microenvironment (e.g., TAMs, CAFs, CSCs).

Conclusions:

• Epigenetic regulation plays a critical role in modulating the dual role of NO in cancer.
• Understanding these epigenetic mechanisms offers potential therapeutic strategies targeting NO production and its impact on cancer progression and the tumor microenvironment.