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

Abstract

Numerous studies have demonstrated that various microRNAs (miRs) are aberrantly expressed in thyroid cancer and play critical roles in thyroid cancer malignancy. The aberrant expression of miR-592 has frequently been reported in multiple human cancer types; however, its expression profile and functions in thyroid cancer remain poorly understood. Reverse transcription-quantitative polymerase chain reaction was carried out to determine the expression profile of miR-592 in thyroid cancer tissues and cell lines. The regulatory effects of miR-592 upregulation on thyroid cancer cell proliferation, migration, and invasion in vitro, and tumor growth in vivo were investigated using a ccK-8 assay, migration and invasion assays, and a xenograft tumor model, respectively. Furthermore, the mechanisms underlying miR-592-mediated suppression of the aggressive phenotypes of thyroid cancer cells were explored in detail. The results indicated that miR-592 was significantly downregulated in thyroid cancer samples, and its downregulation was associated with lymph node metastasis and tumor-node-metastasis stage. Patients with thyroid cancer and low miR-592 expression exhibited shorter overall survival than patients with high miR-592 expression. Overexpression of miR-592 resulted in decreased cell proliferation, migration, and invasion in thyroid cancer. In addition, neuro-oncological ventral antigen 1 (NOVA1) was identified as a novel target gene of miR-592 in thyroid cancer cells. Furthermore, ectopic NOVA1 expression may effectively abolish the tumor-suppressing effects of miR-592 overexpression in thyroid cancer cells. Notably, the lncRNA NEAT1 was proposed to function as a sponge of miR-592 in thyroid cancer cells, thereby regulating NOVA1 expression. Finally, resuming miR-592 expression significantly impaired thyroid cancer tumor growth in vivo. The results indicated that the NEAT1/miR-592/NOVA1 pathway may play regulatory roles in thyroid cancer malignancy in vitro and in vivo. Our findings may provide novel insight into the pathogenesis of thyroid cancer. Therefore, this pathway may be an effective target for treating patients with this disease.

lncRNA NEAT1 ameliorates LPS‑induced inflammation in MG63 cells by activating autophagy and suppressing the NLRP3 inflammasome

“…Nuclear enriched abundant transcript 1 (NEAT1) is a classic lncRNA that is specifically located in paraspeckles and functions as an essential structural determinant by interacting with members of the Drosophila behavior human splicing (DBHS) family of proteins (32)(33)(34)(35). Recently, emerging evidence has suggested that NEAT1 is intricately associated with inflammation.…”

Effects of CDK6 regulated by miR‑298 on proliferation and apoptosis of thyroid cancer cells

“…Thyroid cancer is a common malignant tumor of the endocrine system, its incidence keeps increasing year by year driven by the change of social environment (1). However, due to the latent onset of thyroid cancer, many patients are diagnosed with metastasis, hazarding the prognosis of patients (2,3). The fact that the current diagnosis and treatment of thyroid cancer offer few options results in unsatisfactory therapeutic effect for many patients (4).…”

Long Noncoding RNA CCDC26 Promotes Thyroid Cancer Malignant Progression via miR-422a/EZH2/Sirt6 Axis

“… 42 MiRNA-592 suppresses thyroid cancer development by downregulating NOVA1 and controlling lncRNA NEAT1. 43 MiRNA-15 mediates thyroid cancer invasion, migration, and proliferation by regulating Bcl-2. 44 It has been identified that miR-422a participates in thyroid cancer modulation.…”