Downregulation of miR‑193a‑3p via targeting cyclin D1 in thyroid cancer

Abstract

Thyroid cancer (Tc) is a frequently occurring malignant tumor with a rising steadily incidence. microrna (mirna/mir)-193a-3p is an mirna that is associated with tumors, playing a crucial role in the genesis and progression of various cancers. However, the expression levels of mir-193a-3p and its molecular mechanisms in Tc remain to be elucidated. The present study aimed to probe the expression of miR-193a-3p and its clinical significance in TC, including its underlying molecular mechanisms. Microarray and rna sequencing data gathered from three major databases, specifically Gene expression omnibus (Geo), arrayexpress and The cancer Genome atlas (TcGa) databases, and the relevant data from the literature were used to examine mir-193a-3p expression. Meta-analysis was also conducted to evaluate the association between clinicopathological parameters and mir-193a-3p in 510 Tc and 59 normal samples from the TcGa database. mirWalk 3.0, and the TcGa and Geo databases were used to predict the candidate target genes of mir-193a-3p. Gene ontology, Kyoto encyclopedia of Genes and Genomes and protein-protein interaction network enrichment analyses were conducted by using the predicted candidate target genes to investigate the underlying carcinogenic mechanisms. a dual luciferase assay was performed to validate the targeting regulatory association between the most important hub gene cyclin d1 (ccnd1) and mir-193a-3p. mir-193a-3p expression was considerably downregulated in Tc compared with in the non-cancer controls (P<0.001). The area under the curve of the summary receiver operating characteristic was 0.80. Downregulation of miR-193a-3p was also significantly associated with age, sex and metastasis (P=0.020, 0.044 and 0.048, respectively). Bioinformatics analysis indicated that a low mir-193a-3p expression may augment ccnd1 expression to affect the biological processes of Tc. in addition, ccnd1, as a straightforward target, was validated through a dual luciferase assay. mir-193a-3p and ccnd1 may serve as prognostic biomarkers of Tc. Finally, mir-193a-3p may possess a crucial role in the genesis and progression of Tc by altering the ccnd1 expression.

Tumor suppressor miR‐193a‐3p enhances efficacy of BRAF/MEK inhibitors in BRAF‐mutated colorectal cancer

“…Next, we investigated the protein expression changes to evaluate the molecular mechanisms involved in the induction of apoptosis. We first examined known direct targets of miR‐193a‐3p including KRAS, 29,34‐37 Mcl1, 38,39 Cyclin D1, 40‐44 CDK4 40 and CDK6, 40 and cleaved PARP, 39 an indirectly dysregulated protein by miR‐193a‐3p expression in various cancers. As shown in Figure 2D, miR‐193a‐3p overexpression reduced the protein expressions of KRAS, Mcl1, Cyclin D1, and CDK6 and increased the protein expression of cleaved PARP, compared with NC‐mimic overexpression in LIM1215 and RKO cells.…”

“…The results suggested that ATF2 and MYC are indirectly regulated by miR-193a-3p. Collectively, the tumor-suppressive function of miR-193a-3p is likely attributable to the regulation of several oncogenic pathways through indirect modulation of the expressions of ATF2 and MYC, in addition to that of known direct targets such as KRAS, 29,[34][35][36][37] Mcl1, 38,39 and Cyclin D1 [40][41][42][43][44] (Figure 4E).…”

“…We first examined known direct targets of miR-193a-3p including KRAS, 29,[34][35][36][37] Mcl1, 38,39 Cyclin D1, [40][41][42][43][44]…”

Modern concepts of the molecular pathogenesis of thyroid cancer

“…В исследовании X. Li и соавт. была изучена экспрессия miRNA-193a-3p на материале 510 образцов РЩЖ и 59 фрагментов здоровой ткани ЩЖ [54,55]. Результаты показали, что экспрессия miRNA-193a-3p в клетках РЩЖ была значительно ниже, чем в здоровых клетках (p <0,001).…”

“…Снижение miRNA-193a-3p также было достоверно связано с возрастом, полом и наличием метастазов (p = 0,020; 0,044 и 0,048 соответственно). Биоинформационный анализ данных показал, что низкая экспрессия miRNA-193a-3p может увеличивать экспрессию циклидина D1, который, в свою очередь, активирует пролиферацию и миграцию опухолевых клеток [55].…”