Antisense-miR-21 enhances differentiation/apoptosis and reduces cancer stemness state on anaplastic thyroid cancer

Abstract

Anaplastic thyroid carcinoma (ATC) is the most aggressive malignancy in thyroid cancers. Resistance to current therapies is still a challenge. MicroRNAs are a class of small non-coding RNAs, regulating gene expression. MiR-21 is an oncomiR that is overexpressed in nearly all cancers including ATC. Accumulating evidence suggested that miR-21 has a role in cancer stemness state, apoptosis, cell cycle progression, and differentiation. Therefore, we evaluated the application of Off-miR-21 to sequester the microRNA for therapeutic purposes on ATC cell lines. In this study, C643 and SW1736 were transducted by hsa-miR-21 antagomir (Off-miR-21). PTEN gene expression was performed as a known target of miR-21. Stemness state in cancer stem cells (CSCs) was evaluated by the changes of CSC biomarkers including Oct-4 and ABCG2. Apoptosis was assessed by PDCD4 and Mcl-1 gene expression and flow cytometry. Sodium/iodide symporter (NIS) and thyroglobulin (TG) were measured as ATC differentiation markers. In addition, cell cycle progression was investigated via the alterations of p21 gene expression and flow cytometry. Specific downregulation of miR-21 induced the differentiation and apoptosis in C643 and SW1736. Inversely, the treatment inhibited stemness state and cell cycle progression. Knockdown of miR-21 significantly increased the expression of PDCD4, p21, NIS, and TG while leading to decreased expression of Oct-4, ABCG2, and Mcl-1.Taken together, the results suggest that miR-21, as an oncomiR, has a role not only in stemness state but also in tumor growth, differentiation, and apoptosis. Hence, suppression of miR-21 could pave the way for ATC therapy.

Genetic variant in miR‐21 binding sites is associated with colorectal cancer risk

“…MiR-21 has been reported to be upregulated in various cancers, and it inhibited colorectal cancer cell apoptosis and enhanced cell growth. 12,14,29,30 Our experimental data were almost identical to previously reported literature. Furthermore, we found a significant negative correlation between miR-21 and…”

“…The mutation allele of rs6504593 reduced the binding of miR‐21 to the IGF2BP1 3ʹ‐UTR and increased IGF2BP1 expression, which leads to the initiation of colorectal cancer. MiR‐21 has been reported to be upregulated in various cancers, and it inhibited colorectal cancer cell apoptosis and enhanced cell growth . Our experimental data were almost identical to previously reported literature.…”

miRNA expression and function in thyroid carcinomas: a comparative and critical analysis and a model for other cancers

“…To explain these results, targeted mRNAs such as THRB, PTEN and PDCD4 have been reported as repressed. However, the direct inhibition of these mRNAs by miR-21-5p has only been proved in non-thyroid cell lines [84–87]. On the other hand, Frezzetti et al [88] performed target and pathway bioinformatics analyses based on the modulated mRNAs following an in vitro increase of miR-21-5p expression in thyroid cells.…”

Prognostic Significance of MiRNA in Patients with Diffuse Large B-Cell Lymphoma: a Meta-Analysis

“…Moreover miR-21 targets Sprouty2 resulting in cellular protrusions enhancement and augment of cell proliferation and migration [60]. Several studies in vitro have shown that miR-21 influences tumor cell growth and apoptosis [61][62][63][64]. Thus, miR-21 acting as a negative prognostic biomarker has been widely accepted.…”