MicroRNAs in adrenal tumors: relevance for pathogenesis, diagnosis, and therapy

Abstract

Several lines of evidence support the relevance of microRNAs in both adrenocortical and adrenomedullary (pheochromocytomas) tumors. Significantly differentially expressed microRNAs have been described among benign and malignant adrenocortical tumors and different forms of pheochromocytomas that might affect different pathogenic pathways. MicroRNAs can be exploited as markers of malignancy or disease recurrence. Besides tissue microRNAs, novel data show that microRNAs are released in body fluids, and blood-borne microRNAs can be envisaged as minimally invasive markers of malignancy or prognosis. MicroRNAs might even serve as treatment targets that could expand the rather-limited therapeutic repertoire in the field of adrenal tumors. In this review, we present a critical synopsis of the recent observations made in the field of adrenal tumor-associated microRNAs regarding their pathogenic, diagnostic, and potential therapeutic relevance.

Suggested roles for microRNA in tumors

“…In adrenocortical tumors, we have proposed that miR-483-5p/ miR-483-3p, miR-195, and miR-210 would be the most suitable candidates for treatment targets (12). Modulation of microRNAs might facilitate other anti-tumor treatments, e.g., the up-regulation of miR-195 in breast cancer cells enhanced their sensitivity to adriamycin administration (54), or down-regulation of the main hypoxia-associated miR-210 improved the outcome of radiation therapy in a human hepatoma xenograft model (55).…”

“…A major biological difficulty is related to the tissue specific action of micro-RNA, whereby off-target actions may arise in other organs or tissues with undesirable side effects. If the dose of the administered pre-microRNA is too high, it might saturate the endogenous microRNA processing machinery that might lead to unforeseen complications (12,56).…”

“…Given their basic biological functions, it was not surprising to uncover their relevance in several diseases. The differential expression of microRNA has been described in a wide variety of diseases including cancer (3,12). MicroRNA deregulation is considered to be a major phenomenon of tumor formation (3,4).…”

“…Differential expression of tissue microRNAs can be used for the diagnosis of malignancy or as prognostic markers. Micro-RNA markers of malignancy can be especially useful for the diagnosis of tumors whose histological analysis is difficult [e.g., differentiated thyroid tumors (16,17) and adrenal tumors (12)]. The diagnostic utility of microRNAs is further extended due to their stability, because formalin-fixed, paraffin embedded tissue blocks might also be efficiently used for microRNA analysis (18).…”

Update on microRNA as Biomarkers of Adrenocortical Cancer: Perspective on Circulating microRNA

“…MicroRNAs as biomarkers could be especially useful in tumors whose histological diagnosis is difficult, such as adrenocortical tumors [1,4]. Although benign adrenocortical tumors are common, ACC is rare with an estimated incidence of 0.5-2 cases/ million/year [5].…”