Expression level of NEAT1 differentiates benign and malignant thyroid nodules by regulating NEAT1/miR‑9/PTEN and NEAT1/miR‑124/PDCD6 signalling

Abstract

The incidence of thyroid nodules has been increasing worldwide; however, there are currently no feasible and robust methods to differentiate malignant thyroid nodules from benign thyroid nodules. The present study aimed to establish a practical method to determine the malignancy of thyroid nodules. Reverse transcription-quantitative PcR and western blot analyses were performed to compare the levels of long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1), microRNA (miR)-9, miR-124, PTEN and programmed cell death protein 6 (Pdcd6) in the peripheral blood and thyroid tissue samples between patients with malignant and benign thyroid nodules. Additionally, a regulatory relationship between NEAT1, miR-124, miR-9, PTEN and Pdcd6 was established in the present study. The diagnostic value of NEAT1, miR-124 and miR-9 was determined using a ROc analysis. The expression levels of NEAT1, PTEN and Pdcd6 in peripheral blood and thyroid tissue samples collected from the benign group were higher compared with those in the malignant group, whereas the expression levels of miR-124 and miR-9 were lower in the benign group. In the peripheral blood, NEAT1 expression exhibited an area under the curve (AUc) value of 0.8546, whereas miR-124 and miR-9 expression had AUc values of 0.7657 and 0.7019, respectively. In the thyroid tissue, NEAT1, miR-124, and miR-9 had AUc values of 0.9304, 0.8221 and 0.7757, respectively. Additionally, miR-9 and miR-124 expression levels in BcPaP and SW579 cells was decreased after transfection with a NEAT1 expression vector compared with those in cells transfected with the control vector, whereas the expression of PTEN and Pdcd6 was upregulated. By contrast, transfection with short hairpin RNA targeting NEAT1 notably increased the expression of miR-9 and miR-124 while downregulating the expression of PTEN and Pdcd6 compared with that in the control cells. In conclusion, the results of the present study demonstrated that the dysregulation of NEAT1 expression may be used to differentiate benign and malignant thyroid nodules.

Association of long non-coding RNAs NEAT1, and MALAT1 expression and pathogenesis of Behçet's disease among Egyptian patients

“…In patients with colorectal cancer, NEAT1 showed a significant predictive role in differentiating between patients and normal controls (AUC = 0.9471; P < 0.01) ( Peng et al, 2017 ). A comparable finding was also observed in COPD cases (AUC = 0.869, 95% CI: 0.817–0.921) ( Ming et al, 2019 ), myocardial infarction (AUC = 0.822; P < 0.01) ( Chen et al, 2020 ), and malignant thyroid nodules (AUC = 0.9304, P < 0.01) ( Zhao et al, 2020 ). With respect to MALAT1, many studies have indicated its role in the diagnosis of various diseases, like non-traumatic osteonecrosis of the femoral head (AUC = 0.681, P = 0.009) ( Jin et al, 2020 ), diabetic retinopathy (AUC = 0.741, P < 0.001) ( Shaker et al, 2019a , Shaker et al, 2019b ), and diabetic nephropathy (AUC = 0.914, P < 0.01) ( Zhou et al, 2020 ).…”

Regulation of the Key Epithelial Cancer Suppressor miR-124 Function by Competing Endogenous RNAs

“…Another highly represented in tumors and actively studied lncRNA NEAT1 (nuclear-enriched abundant transcript 1) was regulated in four types of cancer: breast cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, and malignant thyroid nodules [ 81 , 82 , 83 , 84 ]. All these studies were conducted both on cell lines and on clinical samples from patients; xenografts of mice were used in two studies [ 81 , 82 ].…”

“…All these studies were conducted both on cell lines and on clinical samples from patients; xenografts of mice were used in two studies [ 81 , 82 ]. Four interactomes were identified: NEAT1/miR-124-3p/ATGL (adipose triglyceride lipase), NEAT1/miR-124-3p/p65 (NF-κB), NEAT1/miR-124/PDCD6 (programmed cell death 6), NEAT1/miR-124-3p/STAT3 (signal transducer and activator of transcription 3) [ 81 , 82 , 83 , 84 ], which is also shown in Figure 2 b. These interactomes increased cell proliferation, migration, invasion, EMT and inhibit apoptosis in vitro and initiate tumor growth in immune-deficient mice in vivo.…”

RBM10 regulates alternative splicing of lncRNA Neat1 to inhibit the invasion and metastasis of NSCLC

“…In addition, PI3K/AKT/mTOR, as a classic signaling pathway in tumors, is often caused by abnormal PTEN gene function, resulting in inhibition of cell apoptosis, acceleration of cell cycle, promotion of angiogenesis and tumor invasion and metastasis [ 25 – 27 ]. The studies found that Neat1 can inhibit the expression level of PTEN in laryngeal cancer [ 28 ] and thyroid carcinoma [ 29 ] to promote malignant biological behavior of tumors. Previous research by our group also found that RBM10 can regulate RAP1/AKT/CREB to play a tumor suppressor role [ 30 ].…”