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

Abstract

Nitric oxide (NO) has been identified and described as a dual mediator in cancer according to dose-, time- and compartment-dependent NO generation. The present review addresses the different epigenetic mechanisms, such as histone modifications and non-coding RNAs (ncRNAs), miRNA and lncRNA, which regulate directly or indirectly nitric oxide synthase (NOS) expression and NO production, impacting all hallmarks of the oncogenic process. Among lncRNA, HEIH and UCA1 develop their oncogenic functions by inhibiting their target miRNAs and consequently reversing the inhibition of NOS and promoting tumor proliferation. The connection between miRNAs and NO is also involved in two important features in cancer, such as the tumor microenvironment that includes key cellular components such as tumor-associated macrophages (TAMs), cancer associated fibroblasts (CAFs) and cancer stem cells (CSCs).

Iron nitrosyl complexes are formed from nitrite in the human placenta

“…The mechanism may be via posttranslational protein modifications, such as S-nitrosylation and nitration resulting in altered function of transcription factors (35,36) or direct modification of histone protein structure (37). In addition, and particularly relevant to the current observation of FeNO formation, NO has also been shown to modify global histone methylation by inhibiting Jumonji C domaincontaining demethylases through formation of an FeNO complex in the catalytic core of the demethylase enzyme (22,38,39). Our observation that nitrite-derived FeNOs were associated with an increase in histone methylation at a number of lysine residues is in support of a role for FeNOs in epigenetic regulation.…”

Coumarin–Furoxan Hybrid Suppressed the Proliferation and Metastasis of Triple-Negative Breast Cancer by Activating Mitochondrial Stress and Cell Apoptosis

“…NO donor compound anticancer studies could potentially include epigenetics. Future studies could also be extended to the field of epigenetics . Protein kinases play critical roles in cancer development and treatment by modulating protein phosphorylation, a prevalent post-translational modification. , NO stimulates MKP-1 transcription in human breast cancer cells, dephosphorylating Erk and Akt kinase, and apoptosis.…”

Insights into the expression of DNA (de)methylation genes responsive to nitric oxide signaling in potato resistance to late blight disease

“…The NOdonor treatment (SNP) upregulated miR-1, which targeted Hsp-70, triggering apoptosis in osteoblasts. Moreover, the link between NO and the differential expression of numerous miRNAs was previously documented in the progression of various cancers and inflammatory diseases (de la Cruz-Ojeda et al, 2021). Differentiated upregulation of NOS expression is closely linked to antitumoral or oncogenic properties of nitric oxide, which are affected by multiple factors.…”