MicroRNA in Acromegaly: Involvement in the Pathogenesis and in the Response to First-Generation Somatostatin Receptor Ligands

Abstract

Acromegaly is a chronic and systemic disease due to excessive growth hormone and insulin-like growth factor type I caused, in the vast majority of cases, by a GH-secreting pituitary adenoma. About 40% of these tumors have somatic mutations in the stimulatory G protein alpha-subunit 1 gene. The pathogenesis of the remaining tumors, however, is still not fully comprehended. Surgery is the first-line therapy for these tumors, and first-generation somatostatin receptor ligands (fg-SRL) are the most prescribed medications in patients who are not cured by surgery. MicroRNAs are small, non-coding RNAs that control the translation of many mRNAs, and are involved in the post-transcriptional regulation of gene expression. Differentially expressed miRNAs can explain differences in the pathogenesis of acromegaly and tumor resistance. In this review, we focus on the most validated miRNAs, which are mainly involved in acromegaly’s tumorigenesis and fg-SRL resistance, as well as in circulating miRNAs in acromegaly.

The Role of microRNAs in Arsenic-Induced Human Diseases: A Review

“…Therefore, circulating miRNAs were considered biomarkers of disease due to their ability to regulate gene expression in distal cells or organs. 15,18,19…”

“…15−17 Circulating miRNAs were usually transported by apoptotic bodies, extracellular vesicles, and exosomes. 15,87 The previous study reported that exosome miRNA was involved in intercellular communication during carcinogenesis induced by arsenic exposure. 136 Exosome miR-21 secreted from arsenictransformed HBE cells can be transferred into normal HBE cells and regulated many biological events in the recipient cells.…”

“…15−17 Therefore, circulating miRNAs are considered biomarkers of disease and can regulate gene expression in distal cells or organs. 15,18,19 Arsenic is regarded as a carcinogen for humans. 20 The natural or geological causes of arsenic in groundwater are a global problem, seriously affecting human and wildlife health.…”

“…A particular miRNA can target various mRNAs to induce translational repression or RNA degradation, and one mRNA can be regulated by multiple different miRNAs . By modulating gene expression at the post-translational level, miRNAs play a critical role in a series of cellular processes, including apoptosis, − oxidative stress, cell proliferation, , inflammation, , hematopoiesis, , and tumorigenesis. , Importantly, miRNAs not only have an intracellular function but also stably exist in biological fluids such as saliva, cerebrospinal fluid, plasma, serum, gingival fluid, and urine. − Therefore, circulating miRNAs are considered biomarkers of disease and can regulate gene expression in distal cells or organs. ,, …”

Delving into Acromegaly

“…Furthermore, many GH-secreting pituitary adenomas harbor chromosomal alterations such as somatic copy number alterations at extensive sites across the genomes. However, epigenetic mechanisms also appear to play a very important role, and Henriques et al dedicate an excellent review to current knowledge regarding microRNAs (miRNAs) in acromegaly, addressing their mechanisms of action, their potential role as biomarkers in pathological processes, specific miRNAs associated with acromegaly tumorigenesis as well as resistance to first-generation somatostatin analogs [ 7 ]. Several differentially expressed miRNAs are associated with proliferation, invasion, size, and even tumor suppression.…”