MicroRNAs in endocrine tumors.

MicroRNAs (miRNAs) are small, protein noncoding RNAs that regulate gene expression post-transcriptionally. Their role is considered to set the gene expression to the optimal level, or in other words to provide "fine tuning" of gene expression. They regulate essential physiological processes such as differentiation, cell growth, apoptosis and their role is known in tumor development too. At tissue level differential miRNA expression in endocrine disorders including endocrine malignancies has also been reported. A new era of miRNAs-related research started when miRNAs were successfully detected outside of cells, in biofluids, in cell-free environments. Their significant role has been demonstrated in cell-cell communication in tumor biology. Due to their stability circulating miRNAs can serve as potential biomarkers. In common diseases circulating miRNAs can be potentially proposed as screening biomarkers and they are also useful to detect tumor recurrence hence they can be applied in post-surgery follow-up too. MiRNAs as diagnostic markers can also be helpful at tissue level when certain histology diagnosis is challenging. Beside diagnosis, tissue miRNAs have the potential to predict prognosis. Intensive research is carried out regarding endocrine tumors as well in terms of miRNAs. However, until now miRNAs as biomarkers do not applied in routine diagnostics, probably due to the challenging preanalytics. In this review we summarized tissue and circulating miRNAs found in thyroid, adrenal, pituitary and neuroendocrine tumors. We aimed to highlight the most important, selected miRNAs with potential diagnostic and prognostic value both in tissue and circulation. Common miRNAs across different endocrine neoplasms are summarized and miRNAs enriched at 14q31 locus are also highlighted suggesting their general role in tumorigenesis of endocrine glands

Circulating Noncoding RNAs in Pituitary Neuroendocrine Tumors — Two Sides of the Same Coin

Pituitary neuroendocrine tumors (PitNET) are common intracranial neoplasms. While in case of hormone secreting tumors pituitary hormone measurements can be used for monitoring the disease, in non-functional tumors there is a need to discover non-invasive biomarkers. Non-coding RNAs (ncRNAs) are popular biomarker candidates due to their stability and tissue specificity. Among ncRNAs, miRNAs, lncRNAs and circRNAs have been investigated the most in pituitary tumor tissues and in circulation. However, it is still not known whether ncRNAs are originated from the pituitary, or whether they are casually involved in the pathophysiology. Additionally, there is strong diversity among different studies reporting ncRNAs in PitNET. Therefore, to provide an overview of the discrepancies between published studies and to uncover the reasons why despite encouraging experimental data application of ncRNAs in clinical routine has not yet taken hold, in this review available data are summarized on circulating ncRNAs in PitNET. The data on circulating miRNAs, lncRNAs and circRNAs are organized according to different PitNET subtypes. Biological (physiological and pathophysiological) factors behind intra- and interindividual variability and technical aspects of detecting these markers, including preanalytical and analytical parameters, sample acquisition (venipuncture) and type, storage, nucleic acid extraction, quantification and normalization, which reveal the two sides of the same coin are discussed

Mechanisms Behind Context-Dependent Role of Glucocorticoids in Breast Cancer Progression

Glucocorticoids (GCs), mostly dexamethasone (dex), are routinely administered as adjuvant therapy to manage side effects in breast cancer. However, recently, it has been revealed that dex triggers different effects and correlates with opposite outcomes depending on the breast cancer molecular subtype. This has raised new concerns regarding the generalized use of GC and suggested that the context-dependent effects of GCs can be taken into potential consideration during treatment design. Based on this, attention has recently been drawn to the role of the glucocorticoid receptor (GR) in development and progression of breast cancer. Therefore, in this comprehensive review, we aimed to summarize the different mechanisms behind different context-dependent GC actions in breast cancer by applying a multilevel examination, starting from the association of variants of the GR-encoding gene to expression at the mRNA and protein level of the receptor, and its interactions with other factors influencing GC action in breast cancer. The role of GCs in chemosensitivity and chemoresistance observed during breast cancer therapy is discussed. In addition, experiences using GC targeting therapeutic options (already used and investigated in preclinical and clinical trials), such as classic GC dexamethasone, selective glucocorticoid receptor agonists and modulators, the GC antagonist mifepristone, and GR coregulators, are also summarized. Evidence presented can aid a better understanding of the biology of context-dependent GC action that can lead to further advances in the personalized therapy of breast cancer by the evaluation of GR along with the conventional estrogen receptor (ER) and progesterone receptor (PR) in the routine diagnostic procedure. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10555-022-10047-1

Wnt-Signaling Regulated by Glucocorticoid-Induced miRNAs

Glucocorticoids (GCs) are pleiotropic hormones which regulate innumerable physiological processes. Their comprehensive effects are due to the diversity of signaling mechanism networks. MiRNAs, small, non-coding RNAs contribute to the fine tuning of signaling pathways and reciprocal regulation between GCs and miRNAs has been suggested. Our aim was to investigate the expressional change and potential function of GC mediated miRNAs. The miRNA expression profile was measured in three models: human adrenocortical adenoma vs. normal tissue, steroid-producing H295R cells and in hormonally inactive HeLa cells before and after dexamethasone treatment. The gene expression profile in 82 control and 57 GC-affected samples was evaluated in GC producing and six different GC target tissue types. Tissue-specific target prediction (TSTP) was applied to identify the most relevant miRNA−mRNA interactions. Glucocorticoid treatment resulted in cell type-dependent miRNA expression changes. However, 19.5% of the influenced signaling pathways were common in all three experiments, of which the Wnt-signaling pathway seemed to be the most affected. Transcriptome data and TSTP showed similar results, as the Wnt pathway was significantly altered in both the GC-producing adrenal gland and all investigated GC target tissue types. In different cell types, different miRNAs led to the regulation of similar pathways. Wnt signaling may be one of the most important signaling pathways affected by hypercortisolism. It is, at least in part, regulated by miRNAs that mediate the glucocorticoid effect. Our findings on GC producing and GC target tissues suggest that the alteration of Wnt signaling (together with other pathways) may be responsible for the leading symptoms observed in Cushing’s syndrome