Mitochondria are organelles responsible for several functions involved in cellular balance, including energy generation and apoptosis. For decades now, it has been well-known that mitochondria have their own genetic material (mitochondrial DNA), which is different from nuclear DNA in many ways. More recently, studies indicated that, much like nuclear DNA, mitochondrial DNA is regulated by epigenetic factors, particularly DNA methylation and non-coding RNAs (ncRNAs). This field is now called mitoepigenetics. Additionally, it has also been established that nucleus and mitochondria are constantly communicating to each other to regulate different cellular pathways. However, little is known about the mechanisms underlying mitoepigenetics and nuclei–mitochondria communication, and also about the involvement of the ncRNAs in mitochondrial functions and related diseases. In this context, this review presents the state-of-the-art knowledge, focusing on ncRNAs as new players in mitoepigenetic regulation and discussing future perspectives of these fields.

Background: The biological role of microRNAs (miRNAs) in field cancerization is unknown. To investigate the involvement of miRNAs in gastric field cancerization, we evaluated the expression profile of ten miRNAs and their diagnostic value.

The theory of field effect suggests that the tumor-adjacent area, besides histopathologically normal, undergoes genetic and epigenetic changes that can eventually affect epithelial homeostasis, predisposing the patient to cancer development. One of the many molecular changes described in cancer are microRNAs (miRNAs), which regulates the expression of important genes during carcinogenesis. Thus, the aim of this study was to investigate the field effect in oral cancer. We investigated the differential expression profile of four miRNAs (hsa-miR-221, hsa-miR-21, hsa-miR-135b, and hsa-miR-29c) in cancerous oral tissue, in tumor-adjacent tissue and and in non-cancerous tissue samples from healthy volunteers. Our results showed significant overexpression profiles of all four studied miRNAs in cancerous oral tissue compared to non-cancerous samples, as well as in tumor-adjacent tissue compared to cancer-free tissue. No significant difference was found when comparing the expression profile of cancerous and tissue-adjacent tissue groups. We found a negative correlation between the expression of hsa-miR-21 expression and STAT3 in oral squamous cell carcinoma. These results suggest that the tissue adjacent to cancer cannot be considered a normal tissue because its molecular aspects are significantly altered. Our data corroborates the hypothesis of field cancerization.

Circular RNAs are a class of long noncoding RNA that were recently rediscovered as diverse, highly abundant, conserved and naturally occurring RNAs in eukaryotes. They are characterized by their 5′...

Field effect in cancer, also called “field cancerization”, attempts to explain the development of multiple primary tumors and locally recurrent cancer. The concept of field effect in cancer has been reinforced, since molecular alterations were found in tumor-adjacent tissues with normal histopathological appearances. With the aim of investigating field effects in gastric cancer (GC), we conducted a high-throughput sequencing of the miRnome of four GC samples and their respective tumor-adjacent tissues and compared them with the miRnome of a gastric antrum sample from patients without GC, assuming that tumor-adjacent tissues could not be considered as normal tissues. The global number of miRNAs and read counts was highest in tumor samples, followed by tumor-adjacent and normal samples. Analyzing the miRNA expression profile of tumor-adjacent miRNA, hsa-miR-3131, hsa-miR-664, hsa-miR-483, and hsa-miR-150 were significantly downregulated compared with the antrum without tumor tissue ( P-value < 0.01; fold-change < 5). Additionally, hsa-miR-3131, hsa-miR-664, and hsa-miR-150 were downregulated ( P-value < 0.001) in all paired samples of tumor and tumor-adjacent tissues, compared with antrum without tumor mucosa. The field effect was clearly demonstrated in gastric carcinogenesis by an epigenetics-based approach, and potential biomarkers of the GC field effect were identified. The elevated expression of miRNAs in adjacent tissues and tumors tissues may indicate that a cascade of events takes place during gastric carcinogenesis, reinforcing the notion of field effects. This phenomenon seems to be linked to DNA methylation patterns in cancer and suggests the involvement of an epigenetic network mechanism.

AIM: To investigate the expression profiles of hsa-miR-29c and hsa-miR-135b in gastric mucosal samples and their values as gastric carcinogenesis biomarkers. METHODS: The expression levels of hsa-miR-29c and hsa-miR-135b in normal gastric mucosa, non-atrophic chronic gastritis, intestinal metaplasia and intestinal-type gastric adenocarcinoma were analysed using quantitative real-time PCR. The difference between hsa-miR-29c and hsa-miR-135b expression profiles in the grouped samples was evaluated by ANOVA and Student’s t-test tests. The results were adjusted for multiple testing by using Bonferroni’s correction. P values ≤ 0.05 were considered statistically significant. To evaluate hsa-miR-29c and hsa-miR-135b expressions as potential biomarkers of gastric carcinogenesis, we performed a receiver operating characteristic curve analysis and the derived area under the curve, and a Categorical Principal Components Analysis. In silico identification of the genetic targets of hsa-miR-29c and hsa-miR-135b was performed using different prediction tools, in order to identify possible genes involved in gastric carcinogenesis. RESULTS: The expression levels of hsa-miR-29c were higher in normal gastric mucosal samples, and decreased progressively in non-atrophic chronic gastritis samples, intestinal metaplasia samples and intestinal-type gastric adenocarcinoma samples. The expression of hsa-miR-29c in the gastric lesions showed that non-atrophic gastritis have an intermediate profile to gastric normal mucosa and intestinal-type gastric adenocarcinoma, and that intestinal metaplasia samples presented an expression pattern similar to that in intestinal-type gastric adenocarcinoma. This microRNA (miRNA) has a good discriminatory accuracy between normal gastric samples and (1) intestinal-type gastric adenocarcinoma; and (2) intestinal metaplasia, and regulates the DMNT3A oncogene. hsa-miR-135b is up-regulated in non-atrophic chronic gastritis and intestinal metaplasia samples and down-regulated in normal gastric mucosa and intestinal-type gastric adenocarcinoma samples. Non-atrophic chronic gastritis and intestinal metaplasia are significantly different from normal gastric mucosa samples. hsa-miR-135b expression presented a greater discriminatory accuracy between normal samples and gastric lesions. This miRNA was associated with Helicobacter pylori presence in non-atrophic chronic gastritis samples and regulates the APC and KLF4 tumour suppressor genes. CONCLUSION: Our results provide evidence of epigenetic alterations in non-atrophic chronic gastritis and intestinal metaplasia and suggest that hsa-miR-29c and hsa-miR-135b are promising biomarkers of gastric carcinogenesis.