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.

<p>Long Noncoding RNA <em>ZFPM2-AS1</em> Enhances the Malignancy of Cervical Cancer by Functioning as a Molecular Sponge of microRNA-511-3p and Consequently Increasing FGFR2 Expression</p>

“…The binding between ZFPM2-AS1 and miR-511-3p in cervical cancer cells was examined by the RIP assay based on the Magna RIP RNA-Binding Protein Immunoprecipitation Kit (Millipore, Bedford, MA, USA), as described by previous study. 34…”

Knockdown of lncRNA NEAT1 suppresses hypoxia-induced migration, invasion and glycolysis in anaplastic thyroid carcinoma cells through regulation of miR-206 and miR-599

“…Similarly, our data validated that hypoxia induced NEAT1 expression in ATC cells in a time-dependent manner. Considering the enhancement of NEAT1 on ATC chemoresistance [17], we assumed the essential involvement of NEAT1 in ATC progression under hypoxia, and our data for the first time uncovered that NEAT1 depletion weakened ATC cell migration and invasion under hypoxia. Hypoxia is widely accepted to trigger the reprogramming of cancer metabolism, leading to increased glucose consumption and lactate production [26].…”

“…Previous documents had also reported that NEAT1 was up-regulated in papillary thyroid cancer (PTC) tissues and cells, and its deficiency repressed PTC progression through the inhibition of cell proliferation, migration, and invasion [15,16]. Moreover, recent research uncovered that NEAT1 was highly expressed in ATC tissues and cells, and a low high of NEAT1 sensitized ATC cell to cisplatin [17]. Herein, in this study, we focused on the role of NEAT1 on ATC cell migration, invasion, and glycolysis under hypoxia and underlying mechanisms governing it.…”

Long non-coding RNA CASC2 enhances cisplatin sensitivity in oral squamous cell cancer cells by the miR-31-5p/KANK1 axis

“…LncRNAs have been reported to be possessed hope as prospective new targets for the treatment of OSCC [44]. It had been pointed out that CASC2 curbed the progressio n of OSCC [16,35]. Also, CASC2 was associated with the chemo-resistance of multifarious tumors [13,[45][46][47].…”