Abstract
BackgroundLong noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) exhibits an oncogenic role in multiple cancers, including gastric cancer (GC). But, the functions of NEAT1 in modulating radio-sensitivity of GC and its potential molecular mechanisms have not been totally elucidated.MethodsqRT-PCR was performed to detect the expressions of NEAT1 and microRNA-27b-3p (miR-27b-3p). Kaplan–Meier survival curves for NEAT1 expression in GC created using KM Plotter. Colony formation assay was used to determine the survival fraction. Cell apoptosis was evaluated by flow cytometry. Luciferase reporter assay was used to verify the relationship between miR-27b-3p and NEAT1.ResultsNEAT1 was highly expressed while miR-27b-3p was downregulated in GC tissues and cells. NEAT1 was negatively correlated with that of miR-27b-3p and associated with poor overall survival. Moreover, NEAT1 and miR-27b-3p varied inversely after radiation in GC tissues and cells. Loss of NEAT1 or upregulation of miR-27b-3p increased the effect of radiation on cell survival fraction inhibition and apoptosis promotion. In addition, NEAT1 negatively regulated the expression of miR-27b-3p in GC cells. Interestingly, the depletion of miR-27b-3p dramatically attenuated the NEAT1 knockdown-mediated function in AGS and MKN-45 cells treated with radiation in vitro. Similarly, downregulation of NEAT1 enhanced the radiation-mediated inhibition of tumor growth, which was mitigated by decrease of miR-27b-3p.ConclusionNEAT1 depletion enhanced radio-sensitivity of GC by negatively regulating miR-27b-3p in vitro and in vivo.
Highlights
Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) exhibits an oncogenic role in multiple cancers, including gastric cancer (GC)
The expression of NEAT1 was increased in GC tissues and was associated with radiation resistance To examine whether NEAT1 participates in the regulation of GC radiosensitivity, the expression of NEAT1 in 31 GC patients was detected
We evaluated the expression of NEAT1 in Human gastric epithelium cell GES-1 and GC cell lines (NCI-N87, SGC-7901, MKN-45, and AGS)
Summary
Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) exhibits an oncogenic role in multiple cancers, including gastric cancer (GC). A previous study revealed that taurine-upregulated gene 1 (TUG1) is required for the cell metastasis of human bladder cancer [12] They further disclosed that TUG1 promotes radio-resistance through miR-145/ZEB2 axis. MALAT1 knockdown increases the sensitization of NPC cells to radiation Those data lncRNAs may be responsible for the modulation of radiotherapy of cancers. LncRNA nuclear-enriched abundant transcript 1 (NEAT1) was reported to be overexpressed in GC cell lines and tissues [14]. They provided the evidence that the high level of NEAT1 is associated with clinical stage, histological type, lymph node metastasis, and distant metastasis of GC. The role of miR-27b-3p in radio-sensitivity of GC is still on the brink of realization
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