MiRNAs as Noninvasive Biomarkers and Therapeutic Agents of Pituitary Adenomas

Abstract

Pituitary adenoma (PA) accounts for 10–15% of all intracranial neoplasms. Even though most pituitary adenomas are benign, it is known that almost 35% of them exhibit an aggressive clinical course, including rapid proliferative activity and invasion of neighboring tissues. MicroRNAs (miRNAs) are short single-stranded RNA molecules that can influence post-transcriptional regulation by controlling target genes. Based on research data on miRNAs over the past 20 years, more than 60% of genes encoding human proteins are regulated by miRNAs, which ultimately control basic cellular mechanisms, including cell proliferation, differentiation, and apoptosis. Dysregulation of miRNAs has been observed in a number of diseases, especially tumors like PA. A majority of miRNAs are expressed within the cells themselves. However, the circulating miRNAs can be detected in several biological fluids of the human body. The identification of circulating miRNAs as new molecular markers may increase the ability to detect a tumor, predict the course of a disease, plan to choose suitable treatment, and diagnose at the earliest signs of impending neoplastic transformation. Therapy of PAs with aggressive behavior is a complex task. When surgery and chemotherapy fail, radiotherapy becomes the treatment of choice against PAs. Therefore, the possibility of implementing circulating miRNAs as innovative diagnostic and therapeutic agents for PA is one of the main exciting ideas.

Identification of significant genes with invasive promotion in non-functional pituitary adenoma via bioinformatical analysis

“…According to reports, p38MAPK can promote the migration and metastasis of BRAF mutant melanoma by inducing PMCA4 degradation. [11] PMCA2 is enriched in basal breast cancer. Silencing PMCA2 can reduce the proliferation of breast cancer cells, thereby silencing the isoforms PMCA1 and PMCA4.…”

Differential non-coding RNAs expression profiles of invasive and non-invasive pituitary adenomas

“…In addition, repeated surgery and sampling in order to define the real molecular profile of the tumor progression is not always possible. Liquid biopsy is a real-time sampling of biomarkers from biofluids such as ncRNAs [ 37 , 38 ]. Liquid biopsy appears as a promising approach to non-invasive detection, molecularly characterized, and monitoring central nervous system (CNS) tumors progression and invasive PAs in particular.…”

“…In this regard, the development of new screening methods, including the detection of molecular biomarkers of early stages of tumorigenesis, is of great importance. In this scenario, it is reasonable to assume that tumor progression will increase the expression level of certain oncogenic circulating ncRNAs, for example, in the bloodstream, in patients with invasive PA [ 37 , 38 ]. As a result, circulating miR-200a and lncRNA ANRIL are becoming candidates of emerging non-invasive biomarkers for invasive PA.…”

Essential Role of the 14q32 Encoded miRNAs in Endocrine Tumors

“…Palumbo et al identified 17 miRNAs to be differentially expressed in GH-producing pituitary tumors; however, none were encoded at 14q32 [ 138 ]. Pituitary tumor-transforming 1 ( PTTG1 ) was identified as a target of miR-126 and miR-381 encoded at 14q32 cluster [ 139 ]. Also, Liang et al demonstrated that overexpression of 4 14q32 miRNAs (miR-655, miR-300, miR-381 and miR-329) inhibited proliferation, migration and invasion, but induced apoptosis in GH3 and MMQ rat pituitary cells and regulated the PTTG1 expression [ 90 ].…”