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LncRNA NEAT1 enhances the resistance of anaplastic thyroid carcinoma cells to cisplatin by sponging miR?9?5p and regulating SPAG9 expression.

ABSTRACT: Anaplastic thyroid carcinoma (ATC) has a poor prognosis due to its resistance to all conventional treatments. The long non?coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) serves a critical role in cancer chemoresistance; however, whether NEAT1 is associated with chemoresistance of ATC remains unclear. In the present study, reverse transcription?quantitative PCR assays were performed to detect the expression levels of NEAT1, microRNA (miR)?9?5p and sperm?associated antigen 9 (SPAG9). Western blot analysis was conducted to assess the protein expression levels of p62, microtubule?associated proteins 1A/1B light chain 3B and SPAG9. Cell proliferation was detected using the Cell Counting kit?8 assay, and cell apoptosis was determined by flow cytometry. Dual?luciferase reporter and RNA immunoprecipitation assays were performed to verify the interaction between NEAT1 and miR?9?5p, or miR?9?5p and SPAG9. Furthermore, an animal model was used to investigate the regulatory effects of NEAT1 on cisplatin (DDP)?resistance in tumors in vivo. The present results demonstrated that NEAT1 was upregulated in ATC tissues and cell lines, and NEAT1 silencing resulted in decreased DDP?resistance of ATC cells. In addition, NEAT1 suppressed miR?9?5p expression by binding to miR?9?5p and SPAG9 was a direct target of miR?9?5p. miR?9?5p overexpression sensitized ATC cells to DDP. Notably, NEAT1 silencing exerted its inhibitory effect on DDP?resistance of ATC via the miR?9?5p/SPAG9 axis in vitro and in vivo. In conclusion, the present study demonstrated that NEAT1 silencing ameliorated DDP?resistance of ATC, at least in part by reducing miR?9?5p sponging and regulating SPAG5 expression; therefore, NEAT1 may be considered a potential therapeutic target of ATC.

SUBMITTER: Yan P

PROVIDER: S-EPMC6776185 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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LncRNA NEAT1 enhances the resistance of anaplastic thyroid carcinoma cells to cisplatin by sponging miR‑9‑5p and regulating SPAG9 expression.

Yan Pei P Su Zijie Z Zhang Zhenhua Z Gao Teng T

International journal of oncology 20190904 5

Anaplastic thyroid carcinoma (ATC) has a poor prognosis due to its resistance to all conventional treatments. The long non‑coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) serves a critical role in cancer chemoresistance; however, whether NEAT1 is associated with chemoresistance of ATC remains unclear. In the present study, reverse transcription‑quantitative PCR assays were performed to detect the expression levels of NEAT1, microRNA (miR)‑9‑5p and sperm‑associated antigen 9 ...[more]

PMID: 31485599

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Project description: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.

Dataset Information

LncRNA NEAT1 enhances the resistance of anaplastic thyroid carcinoma cells to cisplatin by sponging miR?9?5p and regulating SPAG9 expression.

Publications

LncRNA NEAT1 enhances the resistance of anaplastic thyroid carcinoma cells to cisplatin by sponging miR‑9‑5p and regulating SPAG9 expression.

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