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DLX6 Antisense RNA 1 Modulates Glucose Metabolism and Cell Growth in Gastric Cancer by Targeting microRNA-4290

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Abstract

Background

Gastric cancer (GC) is one of the most commonly diagnosed malignancy worldwide. DLX6 antisense RNA 1 (DLX6-AS1) is a long noncoding RNA (lncRNA) that exhibits oncogenic effects on multiple human carcinomas.

Aims

This study aimed to investigate the regulatory effect of DLX6-AS1 in GC progression.

Methods

The expression of DLX6-AS1 in GC tissues and cell lines was examined. The cell viability, number of clones, and apoptosis, aerobic glycolysis, and mitochondrial respiration was assessed. The effect of DLX6-AS1 on tumor growth in nude mice was also evaluated.

Results

DLX6-AS1 was overexpressed in GC tissues and cell lines. DLX6-AS1 knockdown by short hairpin RNA (shRNA) significantly inhibited cell viability and colony formation, and induced apoptosis. DLX6-AS1 silencing impaired aerobic glycolysis but stimulated mitochondrial respiration in GC cells. miR-4290 was confirmed as a downstream target of DLX6-AS1, and their expression levels were inversely correlated. GC cells expressing sh-DLX6-AS1 showed significantly lower level of 3-phosphoinositide-dependent protein kinase 1 (PDK1), a target of miR-4290, compared to cells expressing control shRNA. In addition, the suppressed GC cell malignancy upon DLX6-AS1 knockdown could be prominently reversed by PDK1 overexpression. Meanwhile, PDK1 overexpression enhanced aerobic glycolysis but repressed mitochondrial respiration under sh-DLX6-AS1 treatment. Furthermore, DLX6-AS1 knockdown significantly delayed the tumor growth in a mouse xenograft model inoculated with GC cells.

Conclusions

LncRNA DLX6-AS1 regulated tumor growth and aerobic glycolysis in GC by targeting miR-4290 and PDK1, suggesting DLX6-AS1 might serve as a novel potential therapeutic target for GC treatment from bench to clinic.

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Availability of data and materials

All data generated or analyzed during this study are included in this published article.

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Authors and Affiliations

  1. Department of Gastric, The Affiliated Huaian N0.1 People’s Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huaiyin District, Huai’an City, 223300, Jiangsu Province, China

    Yan Qian, Xu Wu, Guowei Hou, Haixiao Wang, Xiao Hang & Tianfang Xia

  2. Department of Gastroenterology, The Affiliated Huaian N0.1 People’s Hospital of Nanjing Medical University, Huai’an City, 223300, Jiangsu Province, China

    Wei Song

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  1. Yan Qian
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Contributions

YQ and TFX conceived and designed the experiments, WS and XW analyzed and interpreted the results of the experiments, GWH, HXW and XH performed the experiments.

Corresponding author

Correspondence to Tianfang Xia.

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Conflict of interest

The authors declare that they have no conflict of interest, and all authors should confirm its accuracy.

Human and animal rights statement

All experimental protocols were approved by the Ethics Committee of the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University and performed following the World Medical Association Declaration of Helsinki. All animal experimental procedures were approved by the Animal Care and Use Committee of the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University and were performed under the Guide for the Care and Use of Laboratory Animals.

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Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article. All the patients signed written informed consent.

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Cite this article

Qian, Y., Song, W., Wu, X. et al. DLX6 Antisense RNA 1 Modulates Glucose Metabolism and Cell Growth in Gastric Cancer by Targeting microRNA-4290. Dig Dis Sci 66, 460–473 (2021). https://doi.org/10.1007/s10620-020-06223-4

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  • DOI: https://doi.org/10.1007/s10620-020-06223-4

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