Linsong Mu1, Yeli Wang2, Hailong Su1, Yang Lin1, Wu Sui1, Xiang Yu1, Zhongchuan Lv3. 1. Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuding East Rd, Zhifu District, Yantai, 264000, Shangdong, China. 2. Department of Anorectal, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shangdong, China. 3. Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuding East Rd, Zhifu District, Yantai, 264000, Shangdong, China. bexqnf@163.com.
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.
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.