Circular RNA circPOFUT1 enhances malignant phenotypes and autophagy-associated chemoresistance via sequestrating miR-488-3p to activate the PLAG1-ATG12 axis in gastric cancer

被引:25
作者
Luo, Ming [1 ]
Deng, Xiaofeng [1 ]
Chen, Zonglin [1 ]
Hu, Yongjun [1 ]
机构
[1] Cent South Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China
关键词
CISPLATIN; CELLS; CHEMOTHERAPY; GENE;
D O I
10.1038/s41419-022-05506-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Circular RNAs are key regulators in regulating the progression and chemoresistance of gastric cancer (GC), suggesting circular RNAs as potential therapeutic targets for GC. The roles of a novel circular RNA circPOFUT1 in GC are unknown. Here, we found that circPOFUT1 was upregulated in GC tissues and cells, and increased circPOFUT1 expression indicated poor prognosis. Overexpression of circPOFUT1 enhanced cell proliferation, migration, invasion and autophagy-associated chemoresistance in GC, which were suppressed by miR-488-3p overexpression. CircPOFUT1 reduced miR-488-3p expression via sponging miR-488-3p in GC cells. PLAG1 interacted with ATG12 and promoted its expression. MiR-488-3p bound to PLAG1 and suppressed the expression of PLAG1 and ATG12 in GC cells. Overexpression of circPOFUT1 enhanced autophagy-associated chemoresistance of GC cells in vivo, but it was inhibited by overexpression of miR-488-3p. Collectively, circPOFUT1 directly sponged miR-488-3p to activate the expression of PLAG1 and ATG12, thus enhancing malignant phenotypes and autophagy-associated chemoresistance in GC. Our findings show the potential of circPOFUT1 as biomarkers and targeting circPOFUT1 as a therapeutic strategy for GC.
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收藏
页数:13
相关论文
共 39 条
[1]  
Alamri A, 2017, METHODS MOL BIOL, V1606, P265, DOI 10.1007/978-1-4939-6990-6_17
[2]   miR-23b-3p regulates the chemoresistance of gastric cancer cells by targeting ATG12 and HMGB2 [J].
An, Y. ;
Zhang, Z. ;
Shang, Y. ;
Jiang, X. ;
Dong, J. ;
Yu, P. ;
Nie, Y. ;
Zhao, Q. .
CELL DEATH & DISEASE, 2015, 6 :e1766-e1766
[3]   Circular RNAs in Cancer [J].
Bach, Duc-Hiep ;
Lee, Sang Kook ;
Sood, Anil K. .
MOLECULAR THERAPY-NUCLEIC ACIDS, 2019, 16 :118-129
[4]   Update on gastric cancer treatments and gene therapies [J].
Biagioni, Alessio ;
Skalamera, Ileana ;
Peri, Sara ;
Schiavone, Nicola ;
Cianchi, Fabio ;
Giommoni, Elisa ;
Magnelli, Lucia ;
Papucci, Laura .
CANCER AND METASTASIS REVIEWS, 2019, 38 (03) :537-548
[5]   Targeting autophagy to overcome drug resistance: further developments [J].
Chang, Haocai ;
Zou, Zhengzhi .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2020, 13 (01)
[6]   circ_0003418 Inhibits Tumorigenesis And Cisplatin Chemoresistance Through Wnt/β-Catenin Pathway In Hepatocellular Carcinoma [J].
Chen, Hang ;
Liu, Shan ;
Li, Molin ;
Huang, Ping ;
Li, Xiaoping .
ONCOTARGETS AND THERAPY, 2019, 12 :9539-9549
[7]   Inhibition of autophagy promotes cisplatin-induced apoptotic cell death through Atg5 and Beclin 1 in A549 human lung cancer cells [J].
Chen, Jianhua ;
Zhang, Lemeng ;
Zhou, Hui ;
Wang, Wei ;
Luo, Yongzhong ;
Yang, Hua ;
Yi, Huihuang .
MOLECULAR MEDICINE REPORTS, 2018, 17 (05) :6859-6865
[8]   Bioinformatics insight into glycosyltransferase gene expression in gastric cancer: POFUT1 is a potential biomarker [J].
Dong, Shuang ;
Wang, Zhe ;
Huang, Binbin ;
Zhang, Junjie ;
Ge, Yanli ;
Fan, Qilin ;
Wang, Zhirong .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2017, 483 (01) :171-177
[9]   Identification of circRNA-miRNA-mRNA networks contributes to explore underlying pathogenesis and therapy strategy of gastric cancer [J].
Dong, Zhijie ;
Liu, Zhaoyu ;
Liang, Min ;
Pan, Jinhui ;
Lin, Mingzhen ;
Lin, Hai ;
Luo, Yuanwei ;
Zhou, Xinke ;
Yao, Wenxia .
JOURNAL OF TRANSLATIONAL MEDICINE, 2021, 19 (01)
[10]   CircInteractome: A web tool for exploring circular RNAs and their interacting proteins and microRNAs [J].
Dudekulay, Dawood B. ;
Panda, Amaresh C. ;
Grammatikakis, Ioannis ;
De, Supriyo ;
Abdelmohsen, Kotb ;
Gorospe, Myriam .
RNA BIOLOGY, 2016, 13 (01) :34-42