All-Trans Retinoic Acid Rescues the Tumor Suppressive Role of RAR-β by Inhibiting LncHOXA10 Expression in Gastric Tumorigenesis

Abstract

Numerous long noncoding RNAs (LncRNAs) were having recently been shown to be involved in cancer development, including gastric cancer (GC). However, the precise mechanism and treatments to target these molecules have rarely been studied. Thus, we aimed to investigate the function of LncHOXA10 in gastric tumorigenesis and targeted therapy. First, we measured the differences in LncHOXA10 and retinoic acid receptor β (RAR-β) levels in gastric cancer tissues and cell lines compared with those in noncancerous tissues and cell lines. We observed that LncHOXA10 was significantly upregulated in gastric cancer tissues and cell lines, whereas RAR-β showed the opposite trend. Subsequently, loss and gain of LncHOXA10 cell lines were constructed to determine whether LncHOXA10 plays a role in gastric tumorigenesis. The results showed that LncHOXA10 promoted the proliferation, migration, and invasion of cells, whereas apoptosis was markedly inhibited. Subsequently, mechanistic investigations revealed that LncHOXA10 can repress RAR-β expression and that all-trans retinoic acid (ATRA) can rescue the expression of RAR-β. Finally, we showed that ATRA can reverse the pro-cancerous function of LncHOXA10. We showed that LncHOXA10 may be a prognostic and therapeutic factor of gastric cancer by negatively regulating RAR-β. Furthermore, ATRA can inhibit the role of LncHOXA10 in gastric tumorigenesis.

Authors Contribution

Q. H. Zhao and A. L. Hu designed the study. C. Wang conducted the experiments, analyzed the data, and prepared the manuscript. D. D. Zhao, K. X. Wang, L. Gao, Y. He, H. H. Wu, L. Ruan, and W. J. Chen helped in the design, experiments, data collection and analysis, writing. W. S. Yang provided the support of the study design, comments and discussion of the study. D. M. Zhang, T. Xia, S. Q. Qian, Z. N. Liu, and Y. Yang helped in the sampling of biological specimen, the clinical data collection.

Disclosure statement

All authors declare that they have no conflicts of interest.

Additional information

Funding

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