LncRNA HIF1A-AS1 promotes the proliferation of gastric cancer cell lines through interfering with HIF1A

doi:10.16352/j.issn.1001-6325.2025.05.0627

Abstract

Abstract: Objective To investigate the effects of HIF1A-AS1 on the proliferation and apoptosis of gastric cancer cells lines BGC-823 and MKN28 and its possible mechanism. Methods The expression of HIF1A-AS1 in gastric cancer tissues was analyzed by bioinformatics. HIF1A-AS1 over expression and silenced BGC-823 and MKN28 cell strains were constructed. HIF1A-AS1 expression was detected by real-time PCR, cell proliferation was detected by CCK-8 assay, and apoptosis was detected by flow cytometry. Western blot was used to detect the expression of HIF1A protein in cytoplasm and nucleus and cellular immunofluorescence was used to detect HIF1A protein into nucleus. Results Models of BGC-823 and MKN28 gastric cancer cells with HIF1A-AS1 over-expression and silence were successfully constructed.HIF1A-AS1 over-expression decreased cell proliferation (P＜0.05), while HIF1A-AS1 over-expression significantly increased cell proliferation (P＜0.05). HIF1A-AS1 silencing significantly increased the apoptosis (P＜0.05), and HIF1A-AS1-over expression significantly decreased the apoptosis (P＜0.05). HIF1A-AS1 silencing inhibited the nucleation of HIF1A protein and over-expression promoted the nucleation of HIF1A protein. HIF1A-AS1 silencing significantly decreased the expression of HIF1A cytoplasmic protein (P＜0.05) and over-expression of HIF1A-AS1 significantly increased the expression of HIF1A cytoplasm protein (P＜0.05). HIF1A-AS1 silencing significantly decreased the expression of HIF1A nuclear protein (P＜0.05) while HIF1A-AS1 over-expression significantly increased the expression of HIF1A nuclear protein (P＜0.05). Conclusions HIF1A-AS1 may promote the proliferation and inhibit apoptosis of BGC-823 and MKN28 gastric cancer cells by regulating the expression of parental gene HIF1A.

Key words: parental gene control, enter the nucleus, proliferation, apoptosis

CLC Number:

R73-3

YIN Lijun, BO Yang, Anggelema, SONG Linlin. LncRNA HIF1A-AS1 promotes the proliferation of gastric cancer cell lines through interfering with HIF1A[J]. Basic & Clinical Medicine, 2025, 45(5): 627-636.

References 15

[1]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024,74:229-263. doi: 10.3322/caac.21834.
[2]	Machlowska J, Baj J, Sitarz M, et al. Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies[J]. Int J Mol Sci, 2020,21:4012. doi:10.3390/ijms21114012.
[3]	Yan H, Bu P. Non-coding RNA in cancer[J]. Essays Biochem,2021,65:625-639.
[4]	肖宁,林玮键,龙永福.长链非编码RNA HIF1A-AS1的研究现状与进展[J].现代医学与健康研究电子杂志,2021,5:126-128.
[5]	Hong F, Gao Y, Li Y, et al. Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy[J]. World J Surg Oncol, 2020,18:113.doi: 10.1186/s12957-020-01884-x.
[6]	Xu J, Zhang Y, Chu L, et al. Long non-coding RNA HIF1A-AS1 is upregulated in intracranial aneurysms and participates in the regulation of proliferation of vascular smooth muscle cells by upregulating TGF-β1[J]. Exp Ther Med, 2019,17:1797-1801.doi: 10.3892/etm.2018.7144.
[7]	Gao J, Cao R, Mu H. Long non-coding RNA UCA1 may be a novel diagnostic and predictive biomarker in plasma for early gastric cancer[J]. Int J Clin Exp Pathol, 2015,8:12936-12942.
[8]	Gong Z, Yang J, Dong J, et al. LncRNA HIF1A-AS1 regulates the cellular function of HUVECs by globally regulating mRNA and miRNA expression[J]. Front Biosci (Landmark Ed), 2022,27:330. doi: 10.31083/j.fbl2712330.
[9]	Gong W, Tian M, Qiu H, et al. Elevated serum level of lncRNA-HIF1A-AS1 as a novel diagnostic predictor for worse prognosis in colorectal carcinoma[J]. Cancer Biomark, 2017,20:417-424. doi: 10.3233/CBM-170179.
[10]	Tantai J, Hu D, Yang Y, et al. Combined identification of long non-coding RNA XIST and HIF1A-AS1 in serum as an effective screening for non-small cell lung cancer[J]. Int J Clin Exp Pathol, 2015,8:7887-7895.
[11]	Chen D, Wu L, Liu L, et al. Comparison of HIF1A-AS1 and HIF1A-AS2 in regulating HIF-1α and the osteogenic differentiation of PDLCs under hypoxia[J]. Int J Mol Med, 2017,40:1529-1536. doi: 10.3892/ijmm.2017.3138.
[12]	Tantai J, Hu D, Yang Y, et al. Combined identification of long non-coding RNA XIST and HIF1A-AS1 in serum as an effective screening for non-small cell lung cancer[J]. Int J Clin Exp Pathol, 2015,8:7887-7895.
[19]	张广健,高蕊,付军科,等. 多药耐药基因及缺氧诱导因子-1α在食管癌组织中的表达及其临床意义[J]. 西安交通大学学报(医学版), 2010, 31: 724-727.
[20]	Rashid M, Zadeh LR, Baradaran B, et al. Up-down regulation of HIF-1α in cancer progression[J]. Gene, 2021,798:145796. doi: 10.1016/j.gene.2021.145796.
[14]	Maruggi M, Layng FI, Lemos R Jr, et al. Absence of HIF1A leads to glycogen accumulation and an inflam-matory response that enables pancreatic tumor growth[J]. Cancer Res, 2019,79:5839-5848. doi: 10.1158/0008-5472.CAN-18-2994.
[15]	金烨,颜海豪,代璐,等.缺氧诱导因子-1在胃癌中的研究进展[J].中国临床研究,2021,34:405-408.

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