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Protective effects of all-trans retinoic acid against gastric premalignant lesions by repressing exosomal LncHOXA10–pyruvate carboxylase axis

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Long noncoding RNAs (LncRNAs) play a pivotal role in gastric tumorigenesis, while exosomes facilitate the LncRNAs transferring to recipient cells. However, the roles of exosomal LncRNAs in gastric premalignant lesions (GPL) remain unclear.

Methods

We analyzed the expression of LncHOXA10 and its role in GPL progression. The protective effect of all-trans retinoic acid (ATRA) on GPL was explored in vitro and in vivo.

Results

Here, we found that LncHOXA10 expression was obviously increased in serum exosomes and gastric tissues from individuals with GPL, and exosomal LncHOXA10 from patients with GPL markedly promoted the malignant progression of human gastric epithelial cell line GES-1. Furthermore, RNA-pulldown assay revealed that LncHOXA10 mainly interacted with pyruvate carboxylase (PC), an essential enzyme in various cellular metabolic pathways. In gastric tissues from patients with GPL and gastric cancer (GC), PC was also upregulated and positively correlated with LncHOXA10 expression, which predicted a poor prognosis as well. Moreover, PC silencing attenuated the malignant effects of exosomal LncHOXA10 on GES-1 cells. ATRA also ameliorated the deterioration of GPL and prevented the malignant progression of GPL by reducing exosomal LncHOXA10 and PC expression.

Conclusions

Collectively, the LncHOXA10–PC axis participated in the early stage of GC tumorigenesis, and ATRA might be useful to prevent GPL from developing into GC because it targets this axis.

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Data availability statement

All data are available upon request.

Abbreviations

GPL:

Gastric premalignant lesions

PC:

Pyruvate carboxylase

GC:

Gastric cancer

ATRA:

All-trans retinoic acid

LncRNAs:

Long noncoding RNAs

LncHOXA10:

LncRNA Homeobox A10

Oe control:

Overexpressing control

Oe LncHOXA10:

Overexpressing LncHOXA10

si-PC:

siRNA PC

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Funding

This study was supported by Grants from the National Nature Science Research Grant of China (81502806, 81973049), the University Natural Science Research Project of Anhui Province (No. KJ2019A0227) and Anhui Provincial Natural Science Foundation (No. 1808085MH258).

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Authors

Contributions

ALH and QHZ conceived and designed the study and helped polish the manuscript. CW carried out the experiments, analyzed the data and drafted the manuscript. DDZ, XS, KXW, TTW, and XL conducted a part of the experiments. DMZ and WSY analyzed the experimental data. TX, SQQ, and MT helped in the sampling of biological specimen. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Anla Hu or Qihong Zhao.

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The authors declare that they have no conflict of interest.

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Wang, C., Zhao, D., Shu, X. et al. Protective effects of all-trans retinoic acid against gastric premalignant lesions by repressing exosomal LncHOXA10–pyruvate carboxylase axis. J Cancer Res Clin Oncol 148, 121–135 (2022). https://doi.org/10.1007/s00432-021-03820-2

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