HIF1A-AS2 Promotes the Proliferation and Metastasis of Gastric Cancer Cells Through miR-429/PD-L1 Axis.

Abstract

BACKGROUND:

Gastric cancer (GC) is a common leading cause of cancer-related mortality of all malignancies. LncRNA hypoxia-inducible factor-1 alpha antisense RNA-2 (HIF1A-AS2) has been identified to involve in the development of GC. Therefore, we further explored the detailed molecular mechanism of HIF1A-AS2 in GC progression.

METHODS:

The expression of HIF1A-AS2, microRNA-429 (miR-429), and programmed cell death ligand 1 (PD-L1) was measured using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, migration, and invasion abilities were detected by Cell Counting Kit-8 (CCK-8) or transwell assay. The interaction between miR-429 and HIF1A-AS2 or PD-L1 was confirmed by luciferase reporter assay. Murine xenograft model was established to investigate the role of HIF1A-AS2 in vivo.

RESULTS:

HIF1A-AS2 was elevated in GC tissues and cell lines. Functional experiments showed that HIF1A-AS2 knockdown inhibited GC cell proliferation, migration, and invasion in vitro, as well as hindered tumor growth in vivo. Moreover, HIF1A-AS2 directly bound to miR-429 based on bioinformatics prediction and luciferase assay, and inhibition of miR-429 abolished the effects of HIF1A-AS2 knockdown on GC cells. Furthermore, miR-429 directly targeted PD-L1, and overexpression of miR-429 suppressed GC tumorigenesis via PD-L1. Besides that, PD-L1 also performed an oncogenic role in GC cell proliferation and metastasis. Additionally, HIF1A-AS2 could indirectly regulate PD-L1 expression via sponging miR-429.

CONCLUSION:

HIF1A-AS2 is a dependable predictor of malignancy and prognosis in GC and functions as an oncogene to promote GC cell proliferation and metastasis by regulating miR-429/PD-L1 axis, indicating a new insight into the search for novel biomarkers and therapeutic strategies.

• Authors: Linsong Mu, Yeli Wang, Hailong Su, Yang Lin, Wu Sui, Xiang Yu, Zhongchuan Lv
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 66 Issue 12 Pg. 4314-4325 (12 2021) ISSN: 1573-2568 [Electronic] United States
• PMID: 33555514 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• MIRN429 microRNA, human
• MicroRNAs

Topics

• Animals
• B7-H1 Antigen (metabolism)
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Male
• Mice, Nude
• MicroRNAs (metabolism)
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Transplantation
• Stomach Neoplasms (metabolism, mortality)
• Mice