MicroRNA-1249 Targets G Protein Subunit Alpha 11 and Facilitates Gastric Cancer Cell Proliferation, Motility and Represses Cell Apoptosis

被引:10
作者
Zhang, Hongzhu [1 ]
Fu, Tingting [1 ]
Zhang, Cuiping [2 ]
机构
[1] Jinan Jigang Hosp, Dept Gastroenterol, Jinan 250101, Shandong, Peoples R China
[2] Qingdao Univ, Affiliated Hosp, Dept Gastroenterol, 16 Jiangsu Rd, Qingdao 266000, Shandong, Peoples R China
关键词
gastric cancer; miR-1249; mimic/inhibitor; G protein subunit alpha 11; target; proliferation; apoptosis; PI3K/AKT/mTOR pathway; GNA11; EXPRESSION; MUTATIONS; MIRNAS; GENES;
D O I
10.2147/OTT.S272599
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: The purpose of our study was to investigate the effects of miR-1249 in gastric cancer. Methods: By analyzing the data obtained from TCGA database, the expression and prognosis of miR-1249 in gastric cancer patients were analyzed. Then, CCK8, colony forming and transwell assays were used to test cell proliferation and motility. The cell apoptosis was detected by flow cytometry. The Pearson correlation coefficient analyzed was applied to analyze the correlation between GNA11 and miR-1249. qRT-PCR and Western blotting assays were employed to detect the mRNA and protein levels. Results: We discovered that miR-1249 was highly expressed and was associated with a worse prognosis in gastric cancer patients. Besides, miR-1249 was up-regulated in gastric cancer cell lines (AGS, MKN45 and SNU1). More interestingly, miR-1249 exerted facilitating impacts on gastric cancer cell proliferation and motility, whereas miR-1249 acted as a suppressing effect on gastric cancer apoptosis. G protein subunit alpha 11 (GNA11) was a target gene of miR-1249 and was negatively correlated with miR-1249. Furthermore, GNA11 was negatively regulated by miR-1249. Additionally, GNA11 was lowly expressed in gastric cancer tissues and cell lines, as well as low GNA11 expression, was related to poor overall survival results in gastric cancer patients. The promoting influences of miR-1249 over-expression on AGS cell proliferation and motility was rescued by GNA11 overexpression, which might be achieved by regulating PI3K/AKT/mTOR signalling pathway. Conclusion: Above all, we concluded that miR-1249 was concerned with the progression of gastric cancer through regulating GNA11, suggesting that miR-1249 and GNA11 might serve as predictive biomarkers for gastric cancer therapy.
引用
收藏
页码:1249 / 1259
页数:11
相关论文
共 41 条
[1]  
Armand-Labit Virginie, 2017, BioMolecular Concepts, V8, P61, DOI 10.1515/bmc-2017-0002
[2]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[3]   RETRACTED: Epigenetic silenced miR-125a-5p could be self-activated through targeting Suv39H1 in gastric cancer (Retracted Article) [J].
Cai, Mingzhi ;
Chen, Qiuxian ;
Shen, Juntao ;
Lv, Chenbing ;
Cai, Lisheng .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2018, 22 (10) :4721-4731
[4]   P53-induced miR-1249 inhibits tumor growth, metastasis, and angiogenesis by targeting VEGFA and HMGA2 [J].
Chen, Xiaoxiang ;
Zeng, Kaixuan ;
Xu, Mu ;
Liu, Xiangxiang ;
Hu, Xiuxiu ;
Xu, Tao ;
He, Bangshun ;
Pan, Yuqin ;
Sun, Huiling ;
Wang, Shukui .
CELL DEATH & DISEASE, 2019, 10 (2)
[5]   MicroRNA-1249 targets four-jointed box kinase 1 and reduces cell proliferation, migration and invasion of colon adenocarcinoma [J].
Dang, Wen ;
Zhu, Zhen .
JOURNAL OF GENE MEDICINE, 2020, 22 (07)
[6]   Signaling Pathways Regulating Redox Balance in Cancer Metabolism [J].
De Santis, Maria Chiara ;
Porporato, Paolo Ettore ;
Martini, Miriam ;
Morandi, Andrea .
FRONTIERS IN ONCOLOGY, 2018, 8
[7]   Advanced gastric cancer: Current treatment landscape and future perspectives [J].
Digklia, Antonia ;
Wagner, Anna Dorothea .
WORLD JOURNAL OF GASTROENTEROLOGY, 2016, 22 (08) :2403-2414
[8]  
Fang BJ, 2018, AM J TRANSL RES, V10, P1324
[9]   Dysregulation of microRNA biogenesis and gene silencing in cancer [J].
Hata, Akiko ;
Lieberman, Judy .
SCIENCE SIGNALING, 2015, 8 (368) :re3
[10]   The contrary functions of lncRNA HOTAIR/miR-17-5p/PTEN axis and Shenqifuzheng injection on chemosensitivity of gastric cancer cells [J].
Jia, Jianguang ;
Zhan, Dankai ;
Li, Jing ;
Li, Zhixiang ;
Li, Hongbo ;
Qian, Jun .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2019, 23 (01) :656-669