Simple Summary In our journey to fight cancer, biomarkers for prediction and efficacy of therapies could help medical practitioners to give patients the best available treatments in a timely fashion. Non-coding RNA, in most recent times, has been shown to play crucial roles for cancer growth. An exponential increase of evidence in the clinical literature supports their implication to predict patients’ outcomes. In this article, we summarize the current predictive and prognostic value of non-coding RNA in breast cancer. Abstract For decades since the central dogma, cancer biology research has been focusing on the involvement of genes encoding proteins. It has been not until more recent times that a new molecular class has been discovered, named non-coding RNA (ncRNA), which has been shown to play crucial roles in shaping the activity of cells. An extraordinary number of studies has shown that ncRNAs represent an extensive and prevalent group of RNAs, including both oncogenic or tumor suppressive molecules. Henceforth, various clinical trials involving ncRNAs as extraordinary biomarkers or therapies have started to emerge. In this review, we will focus on the prognostic and diagnostic role of ncRNAs for breast cancer.

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Predictive and Prognostic Value of Non-Coding RNA in Breast Cancer

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, the syndrome is poorly understood and remains underdiagnosed, and female patients are diagnosed with a delay. The heterogenous nature of this complex disorder results from the combined occurrence of genetic, environmental, endocrine, and behavioral factors. Primary clinical manifestations of PCOS are derived from the excess of androgens (anovulation, polycystic ovary morphology, lack of or scanty, irregular menstrual periods, acne and hirsutism), whereas the secondary manifestations include multiple metabolic, cardiovascular, and psychological disorders. Dietary and lifestyle factors play important roles in the development and course of PCOS, which suggests strong epigenetic and environmental influences. Many studies have shown a strong association between PCOS and chronic, low-grade inflammation both in the ovarian tissue and throughout the body. In the vast majority of PCOS patients, elevated values of inflammatory markers or their gene markers have been reported. Development of the vicious cycle of the chronic inflammatory state in PCOS is additionally stimulated by hyperinsulinemia and obesity. Changes in DNA methylation, histone acetylation and noncoding RNA levels are presented in this review in the context of oxidative stress, reactive oxygen species, and inflammatory signaling in PCOS. Epigenetic modulation of androgenic activity in response to inflammatory signaling is also discussed.

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Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)—Searching for Epigenetic Factors

http://www.cell.com/article/S2162253122002785/pdf

Mitochondrion-targeted RNA therapies as a potential treatment strategy for mitochondrial diseases

It has been clear that mitochondria are not just nucleus-relying entities; instead, they also modulate nuclear events reversely. Long noncoding RNAs (lncRNAs) are classified into nuclear-encoded and mitochondrial-derived lncRNAs (nulncRNAs and mtlncRNAs, respectively). Relative to nulncRNAs, the mtlncRNAs are far from being well characterized. Here we report a mtlncRNA, MDL1, that interacts with both p53 and Tid1 proteins and acts as retrograde signaling. MDL1 can regulate a network of nuclear genes, including p53 targets, and functions in cells in a p53-dependent manner. Mechanistically, MDL1 is necessary for maintenance of the reciprocal interaction between p53 and Tid1, thereby facilitating formation of a ternary MDL1/p53/Tid1 complex that inhibits the nuclear translocation of p53. Since p53 is a canonical transcription factor, the observed inhibition of p53 nuclear translocation would contribute to the MDL1-mediated mitochondrial retrograde regulation on nuclear genes expression. This study advances our understanding of lncRNA biology, and also sheds new light on the role of mtlncRNAs in mitochondrial-nuclear functional network and in diverse biological processes. 

The mitochondrial‐derived lncRNA MDL1 mediates a mitochondria‐to‐nucleus retrograde regulation by inhibiting the nuclear translocation of p53

Non-coding RNAs have a role in gene regulation and cellular metabolism control. Metabolism produces metabolites which are small molecules formed during the metabolic process. So far, direct relation between metabolites and genes are not fully established however, pseudogenes and their progenitor genes regulate health and disease states. Other non-coding RNAs also contribute to this regulation at different cellular processes. Accumulation and depletion of metabolites accompany the dynamic equilibrium of health and disease state. In this chapter, metabolites, their roles in the cell, and the link between metabolites and non-coding RNAs are discussed.

Involvement of Metabolites and Non-coding RNAs in Diseases.

Mitochondria are the main hubs for cellular energy production. Metabolites produced in mitochondria not only feed many important biosynthesis pathways but also function as signaling molecules. Mitochondrial biosynthesis requires collaboration of both nuclear and mitochondrial gene expression systems. In addition, mitochondria have to quickly respond to changes inside and outside the cells and have their own functional states reported to the nucleus and other cellular compartments. The underlying molecular mechanisms of these complex regulations have not been well understood. Recent evidence indicates that in addition to small molecules, non-coding RNAs may contribute to the communication between mitochondria and other cellular compartments and may even serve as signals. In this review, we summarize the current knowledge about mitochondrial non-coding RNAs (including nucleus-encoded non-coding RNAs that are imported into mitochondria and mitochondrion-encoded non-coding RNAs that are exported), their trafficking and their functions in co-regulation of mitochondrial and other cellular processes.

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Pengcheng Wang

Papers

Non-coding RNA Regulated Cross-Talk Between Mitochondria and Other Cellular Compartments.