Abstract
Simple SummaryAnaplastic thyroid carcinoma (ATC) is a biological aggressive human carcinoma and causes most of the thyroid cancer related deaths. Non-protein producing RNAs, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play crucial roles in formation and therapy resistance of ATC by regulating the production of key proteins. These RNAs alter the proteome of cells, which in turn controls cancer cells’ growth, division, invasion, migration, metastasis, and recurrence of ATC. Thus, the exogenous manipulation of these RNAs could interfere cells growth and development of ATC. Considering this, we discuss the roles of various miRNAs and lncRNAs in the pathogenesis of ATC and their potential therapeutic applications.Anaplastic thyroid cancer (ATC) remains as one of the most aggressive human carcinomas with poor survival rates in patients with the cancer despite therapeutic interventions. Novel targeted and personalized therapies could solve the puzzle of poor survival rates of patients with ATC. In this review, we discuss the role of non-coding RNAs in the regulation of gene expression in ATC as well as how the changes in their expression could potentially reshape the characteristics of ATCs. A broad range of miRNA, such as miR-205, miR-19a, miR-17-3p and miR-17-5p, miR-618, miR-20a, miR-155, etc., have abnormal expressions in ATC tissues and cells when compared to those of non-neoplastic thyroid tissues and cells. Moreover, lncRNAs, such as H19, Human leukocyte antigen (HLA) complex P5 (HCP5), Urothelial carcinoma-associated 1 (UCA1), Nuclear paraspeckle assembly transcript 1 (NEAT1), etc., participate in transcription and post-transcriptional regulation of gene expression in ATC cells. Dysregulations of these non-coding RNAs were associated with development and progression of ATC by modulating the functions of oncogenes during tumour progression. Thus, restoration of the abnormal expression of these miRNAs and lncRNAs may serve as promising ways to treat the patients with ATC. In addition, siRNA mediated inhibition of several oncogenes may act as a potential option against ATC. Thus, non-coding RNAs can be useful as prognostic biomarkers and potential therapeutic targets for the better management of patients with ATC.
Highlights
Anaplastic thyroid carcinoma (ATC) accounts for 1–2% of all thyroid cancers, it is responsible for the most cancer deaths caused by thyroid cancer despite therapeutic intervention [1,2].ATC is one of the most aggressive solid tumours, which contributes to 3.6% of all human cancers.Many patients with ATC die within a year of diagnosis [3,4,5,6]
Long non-coding RNAs play critical role in ATC by regulating transcription and epigenetic or post-transcriptional regulation of gene expression [16]. They have been found to be implicated in epithelial to mesenchymal transition (EMT) in ATC, which enhances the metastatic potential of ATC
19–25 nucleotides, mediate post-transcriptional gene silencing by partial complementarity with the 30 untranslated region (30 UTR) of the target mRNAs (Figure 1) [17]. miRNAs are one of the most vigorously studied subclasses of non-coding RNAs as they play a regulatory role in epigenetic control of cells [18,19]. miRNA mediated gene silencing occurs through endonucleolytic cleavage or by translational repression [20,21]
Summary
Anaplastic thyroid carcinoma (ATC) accounts for 1–2% of all thyroid cancers, it is responsible for the most cancer deaths caused by thyroid cancer despite therapeutic intervention [1,2]. Genetic, and epigenetic aberrations have been reported to orchestrate the tumourigenesis of ATC [7,8] These aberrations lead to the dysregulation of cellular signalling which as a result enhances cellular proliferation and accelerates tumourigenesis. Many miRNAs are abnormally expressed in thyroid carcinomas These dysregulations in miRNA expression may contribute to the pathophysiology of tumourigenesis and disease progression in ATC [15]. Long non-coding RNAs (lncRNAs) play critical role in ATC by regulating transcription and epigenetic or post-transcriptional regulation of gene expression [16]. They have been found to be implicated in epithelial to mesenchymal transition (EMT) in ATC, which enhances the metastatic potential of ATC. The roles of specific miRNAs, lncRNA, and siRNA molecules in ATC as well as the potential use of ncRNAs in designing targeted therapy against ATC are illustrated
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