GABPA protects against gastric cancer deterioration via negatively regulating GPX1
GABPA is an anti-cancer gene in gastric cancer progression
Abstract
Background: To explore the anti-cancer role of GABPA in the progression of gastric cancer (GC), and the underlying mechanism.
Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression pattern of GABPA in 45 pairs of GC and non-tumoral tissues. The relationship between GABPA expression and clinicopathological indicators of GC patients was analyzed. In AGS and SGC-7901 cells overexpressing GABPA, their migratory ability was determined by transwell and wound healing assay. The interaction between GABPA and its downstream target GPX1 was explored by dual-luciferase reporter assay, and their synergistical regulation on GC cell migration was finally elucidated.
Results: GABPA was downregulated in GC tissues in comparison to normal ones. Low level of GABPA predicted high incidences of lymphatic and distant metastasis in GC. Overexpression of GABPA blocked AGS and SGC-7901 cells to migrate. GABPA could target GPX1 via the predicted binding site. GPX1 was upregulated in clinical samples of GC, and negatively correlated to GABPA level. The anti-cancer effect of GABPA on GC relied on the involvement of GPX1.
Conclusions: GABPA is downregulated in GC samples, which can be utilized to predict GC metastasis. Serving as a tumor suppressor, GABPA blocks GC cells to migrate by targeting GPX1.
References
- Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol 2006; 12(3): 354-62.
- Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev 2014; 23(5): 700-13.
- Song Z, Wu Y, Yang J, Yang D, Fang X. Progress in the treatment of advanced gastric cancer. Tumour Biol 2017; 39(7): 1393375038.
- Digklia A, Wagner AD. Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroenterol 2016; 22(8): 2403-14.
- Song Z, Wu Y, Yang J, Yang D, Fang X. Progress in the treatment of advanced gastric cancer. Tumour Biol 2017; 39(7): 1393375038.
- Aoyama T, Yoshikawa T. Adjuvant therapy for locally advanced gastric cancer. Surg Today 2017; 47(11): 1295-302.
- Tahara T, Arisawa T. DNA methylation as a molecular biomarker in gastric cancer. Epigenomics-Uk 2015; 7(3): 475-86.
- Tang W, Fu K, Sun H, Rong D, Wang H, Cao H. CircRNA microarray profiling identifies a novel circulating biomarker for detection of gastric cancer. Mol Cancer 2018; 17(1): 137.
- Wang J, Liu Y, Sun W, Zhang Q, Gu T, Li G. Plasma exosomes as novel biomarker for the early diagnosis of gastric cancer. Cancer Biomark 2018; 21(4): 805-12.
- Paulsson JO, Wang N, Gao J, Stenman A, Zedenius J, Mu N, et al. GABPA-dependent down-regulation of DICER1 in follicular thyroid tumours. Endocr Relat Cancer 2020:
- Goto S, Takahashi M, Yasutsune N, Inayama S, Kato D, Fukuoka M, et al. Identification of GA-Binding Protein Transcription Factor Alpha Subunit (GABPA) as a Novel Bookmarking Factor. Int J Mol Sci 2019; 20(5):
- Watanabe H, Sawada J, Yano K, Yamaguchi K, Goto M, Handa H. cDNA cloning of transcription factor E4TF1 subunits with Ets and notch motifs. Mol Cell Biol 1993; 13(3): 1385-91.
- Kang YK, Putluri N, Maity S, Tsimelzon A, Ilkayeva O, Mo Q, et al. CAPER is vital for energy and redox homeostasis by integrating glucose-induced mitochondrial functions via ERR-alpha-Gabpa and stress-induced adaptive responses via NF-kappaB-cMYC. Plos Genet 2015; 11(4): e1005116.
- McKelvey BA, Gilpatrick T, Wang Y, Timp W, Umbricht CB, Zeiger MA. Characterization of Allele-Specific Regulation of Telomerase Reverse Transcriptase in Promoter Mutant Thyroid Cancer Cell Lines. Thyroid 2020:
- Helbig S, Wockner L, Bouendeu A, Hille-Betz U, McCue K, French JD, et al. Functional dissection of breast cancer risk-associated TERT promoter variants. Oncotarget 2017; 8(40): 67203-17.
- Guo Y, Yuan X, Li K, Dai M, Zhang L, Wu Y, et al. GABPA is a master regulator of luminal identity and restrains aggressive diseases in bladder cancer. Cell Death Differ 2020; 27(6): 1862-77.
- Helbig S, Wockner L, Bouendeu A, Hille-Betz U, McCue K, French JD, et al. Functional dissection of breast cancer risk-associated TERT promoter variants. Oncotarget 2017; 8(40): 67203-17.
- Yuan X, Mu N, Wang N, Straat K, Sofiadis A, Guo Y, et al. GABPA inhibits invasion/metastasis in papillary thyroid carcinoma by regulating DICER1 expression. Oncogene 2019; 38(7): 965-79.
- Zhang S, Zhang K, Ji P, Zheng X, Jin J, Feng M, et al. GABPA predicts prognosis and inhibits metastasis of hepatocellular carcinoma. Bmc Cancer 2017; 17(1): 380.
- Zeferino RC, Mota N, Grinevicius V, Filipe KB, Sulis PM, Silva F, et al. Targeting ROS overgeneration by N-benzyl-2-nitro-1-imidazole-acetamide as a potential therapeutic reposition approach for cancer therapy. Invest New Drugs 2020; 38(3): 785-99.
- Zhang Q, Xu H, You Y, Zhang J, Chen R. High Gpx1 expression predicts poor survival in laryngeal squamous cell carcinoma. Auris Nasus Larynx 2018; 45(1): 13-9.
- Meng Q, Xu J, Liang C, Liu J, Hua J, Zhang Y, et al. GPx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation. Cell Death Dis 2018; 9(12): 1187.
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