Open AccessMicroRNA-592 suppresses the malignant phenotypes of thyroid cancer by regulating lncRNA NEAT1 and downregulating NOVA1
Author(s) -
Yiqiang Luo,
Tianwei Hao,
Jian Zhang,
Ming Zhang,
Peng Sun,
Lei Wu
Publication year - 2019
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2019.4278
Subject(s) - thyroid cancer , cancer research , oncogene , cancer , metastasis , ectopic expression , microrna , anaplastic thyroid cancer , downregulation and upregulation , biology , thyroid , cancer cell , cell cycle , medicine , endocrinology , cell culture , gene , biochemistry , genetics
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.