MicroRNA Expression in the Progression and Aggressiveness of Papillary Thyroid Carcinoma

Abstract

In the last two decades microRNAs have received great attention in research because of their ability to regulate gene expression. Many studies have shown that defects in different microRNA molecules are linked to many diseases; however, their contribution towards thyroid disease has not been fully explored. Herein, we present a short review of the present state of knowledge on microRNAs, such as their origin, their biogenesis and biological function, as well as their differential expression in papillary thyroid carcinoma. Dysregulated microRNA has been closely linked to thyroid dysfunction and oncogenicity leading to this type of thyroid cancer. The effects of Single Nucleotide Polymorphisms in microRNA are also discussed with respect to papillary thyroid carcinoma.MicroRNAs (miRNA, miR) are a class of endogenous noncoding RNA molecules. Mature miRNAs are short, singlestranded RNA molecules ranging from 18 to 22 nucleotides in length (1). These molecules play a substantial role in the regulation of gene expression, through the induction of translational repression or silencing effects by complementary binding to target mRNAs (2-4). They may also act as tumor suppressor genes and oncogenes (5). Although miRNAs constitute only 3% of the human genome, it is believed that these molecules altogether regulate more than half of the protein-coding genes. Noteworthy, one single miRNA can alter the expression of hundreds of different transcripts (6). MiRNAs are expressed in a tissue-specific fashion (7) and can be found, apart from tissues, also in blood as components of serum, plasma, mononuclear cells and in other body fluids (i.e. urine, semen, saliva, tears, ascitic fluid, amniotic fluid and breast milk) (8, 9). Circulating miRNA molecules are very stable in the blood plasma and serum because they are incorporated in microparticles, such as exosomes and apoptotic bodies (10,11). Biochemical analyses have revealed that miRNA is resistant to RNase activity as well as to extreme acidic and alkaline pH and temperature (12, 13). Biogenesis of microRNAsBriefly, biogenesis of miRNA is initiated by the generation of non-coding primary miRNA (pri-miRNA) transcripts ( 14). MiRNA is first transcribed as pri-miRNA by RNA polymerase II in the nucleus and then, split into precursor microRNA molecules (pre-miRNA) (15). Next, pre-miRNA is transported through exportin 5 (XPO5) to the cytoplasm where it is processed by the Dicer RNase III enzyme, to form mature miRNA (16,17). Mature miRNAs can promote or inhibit mRNA translation and degradation by targeting with precision complementary sequences in 3'UnTranslated Regions (3'UTR) (14,18). In this way, miRNAs modulate different cellular pathways and can be used as therapeutic means to treat pathological conditions, such as cancer (19). Discovery of microRNAsThis novel class of small regulatory RNAs were first described in 1993 by Lee et al. in Caenorhabditis elegans (20). Since their discovery and original description in the 90s, the number of miRNA sequences deposited in the microRNA da...

MicroRNA-592 suppresses the malignant phenotypes of thyroid cancer by regulating lncRNA NEAT1 and downregulating NOVA1

“…Numerous studies have demonstrated that various miRNAs are aberrantly expressed in thyroid cancer and play indispensable roles in the malignancy of thyroid cancer (38-40). Almost all aggressive characteristics of thyroid cancer have been demonstrated to be modulated by miRNAs via regulating the expression of their target genes (41). In the past few decades, multiple miRNAs have been extensively studied in thyroid cancer (13,14,42); however, many miRNAs remain to be investigated.…”

Non-Coding RNAs: Uncharted Mediators of Thyroid Cancer Pathogenesis

“…Shortly after, He et al showed the up-regulation of miR-221, miR-222, and miR-146 in PTC patients, which are the first dysregulated miRNAs reported in thyroid cancer (49). To date, many additional studies have identified miRNAs involved in thyroid cancer initiation and progression (50,51). Here, we summarize the recent list of dysregulated miRNAs in thyroid cancer, published from 2015 onward, with implications in cancer initiation and progression, briefly listed in Table 1.…”

Herbal Active Ingredients: An Emerging Potential for the Prevention and Treatment of Papillary Thyroid Carcinoma

“…During PTC pathogenesis, some critical genes (including BRAF, RET, KRAS, and PI3KCA) through mutation or chromosomal translocation continuously activate their dependent downstream signaling pathways, such as mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/AKT, nuclear factor-κB (NF-κB), and Notch-1, and thereby lead to cellular proliferation, migration, invasion, and angiogenesis [15][16][17]. Recently, emerging clinical trials and experimental researches also demonstrated that some noncoding RNA expressions, such as miRs-21, -34b, -221/222, lncRNA ATB, lncRNA H19, lncRNA HOXA-AS2, circITCH, and circZFR, showed significant association with aggressive clinicopathologic feature in PTC, including tumor size, lymphovascular invasion, lymph node metastases, and presence of BRAF V600E mutation [17][18][19][20][21]. Despite the advances in tumorigenesis, metastasis, and therapy, the underlying mechanism of PTC remains unclear.…”