The novel role of circular RNA ST3GAL6 on blocking gastric cancer malignant behaviours through autophagy regulated by the FOXP2/MET/mTOR axis

被引:29
作者
Xu, Penghui [1 ]
Zhang, Xing [1 ]
Cao, Jiacheng [1 ]
Yang, Jing [1 ]
Chen, Zetian [1 ]
Wang, Weizhi [1 ]
Wang, Sen [1 ]
Zhang, Lu [1 ]
Xie, Li [1 ]
Fang, Lang [1 ]
Xia, Yiwen [1 ]
Xuan, Zhe [1 ]
Lv, Jialun [1 ]
Xu, Hao [1 ,3 ]
Xu, Zekuan [1 ,2 ,3 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Gen Surg, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Nanjing, Peoples R China
[3] Nanjing Med Univ, Collaborat Innovat Ctr Personalized Canc Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Peoples R China
来源
CLINICAL AND TRANSLATIONAL MEDICINE | 2022年 / 12卷 / 01期
基金
中国国家自然科学基金;
关键词
autophagy; circST3GAL6; FOXP2; gastric cancer; transcription factor;
D O I
10.1002/ctm2.707
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Gastric cancer (GC) ranks third in mortality among all cancers worldwide. Circular RNAs (circRNAs) play an important role in the occurrence and development of gastric cancer. Forkhead box P2 (FOXP2), as a transcription factor, is closely associated with the development of many types of tumours. However, the regulatory network between FOXP2 and circRNAs remains to be explored. In our study, circST3GAL6 was significantly downregulated in GC and was associated with poor prognosis in GC patients. Overexpression of circST3GAL6 inhibited the malignant behaviours of GC cells, which was mediated by inducing apoptosis and autophagy. In addition, we demonstrated that circST3GAL6 regulated FOXP2 through the mir-300 sponge. We further found that FOXP2 inhibited MET Proto-Oncogene (MET), which was the initiating factor that regulated the classic AKT/mTOR pathway of autophagy. In conclusion, our results suggested that circST3GAL6 played a tumour suppressive role in gastric cancer through miR-300/FOXP2 axis and regulated apoptosis and autophagy through FOXP2-mediated transcriptional inhibition of the MET axis, which may become a potential target for GC therapy.
引用
收藏
页数:21
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共 45 条
[1]   Predicting effective microRNA target sites in mammalian mRNAs [J].
Agarwal, Vikram ;
Bell, George W. ;
Nam, Jin-Wu ;
Bartel, David P. .
ELIFE, 2015, 4
[2]   Global surveillance of cancer survival 1995-2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2) [J].
Allemani, Claudia ;
Weir, Hannah K. ;
Carreira, Helena ;
Harewood, Rhea ;
Spika, Devon ;
Wang, Xiao-Si ;
Bannon, Finian ;
Ahn, Jane V. ;
Johnson, Christopher J. ;
Bonaventure, Audrey ;
Marcos-Gragera, Rafael ;
Stiller, Charles ;
Azevedo e Silva, Gulnar ;
Chen, Wan-Qing ;
Ogunbiyi, Olufemi J. ;
Rachet, Bernard ;
Soeberg, Matthew J. ;
You, Hui ;
Matsuda, Tomohiro ;
Bielska-Lasota, Magdalena ;
Storm, Hans ;
Tucker, Thomas C. ;
Coleman, Michel P. .
LANCET, 2015, 385 (9972) :977-1010
[3]   LncRNA LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met/Akt/mTOR axis [J].
Cai, Haiping ;
Yu, Yanjiao ;
Ni, Xiangrong ;
Li, Cong ;
Hu, Yuanjun ;
Wang, Jing ;
Chen, Furong ;
Xi, Shaoyan ;
Chen, Zhongping .
CELL DEATH & DISEASE, 2020, 11 (12)
[4]   Foxp3 Re-distributes Its Heavy Lifting [J].
Chandra, Aditi ;
Goldman, Naomi ;
Vahedi, Golnaz .
IMMUNITY, 2020, 53 (05) :895-897
[5]   The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1α translation [J].
Chen, Liang-Yan ;
Wang, Lian ;
Ren, Yue-Xiang ;
Pang, Zheng ;
Liu, Yao ;
Sun, Xiao-Dong ;
Tu, Jian ;
Zhi, Zheng ;
Qin, Yan ;
Sun, Li-Na ;
Li, Jian-Ming .
MOLECULAR CANCER, 2020, 19 (01)
[6]   The independence of and associations among apoptosis, autophagy, and necrosis [J].
Chen, Qi ;
Kang, Jian ;
Fu, Caiyun .
SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2018, 3
[7]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[8]   Identification of glycogene-type and validation of ST3GAL6 as a biomarker predicts clinical outcome and cancer cell invasion in urinary bladder cancer [J].
Dalangood, Sumiya ;
Zhu, Zhen ;
Ma, Zhihui ;
Li, Jiaxuan ;
Zeng, Qinghe ;
Yan, Yilin ;
Shen, Bing ;
Yan, Jun ;
Huang, Ruimin .
THERANOSTICS, 2020, 10 (22) :10078-10091
[9]   Current information on the association of Helicobacter pylori with autophagy and gastric cancer [J].
Eslami, Majid ;
Yousefi, Bahman ;
kokhaei, Parviz ;
Arabkari, Vahid ;
Ghasemian, Abdolmajid .
JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (09) :14800-14811
[10]   CircNR3C2 promotes HRD1-mediated tumor-suppressive effect via sponging miR-513a-3p in triple-negative breast cancer [J].
Fan, Ya ;
Wang, Jia ;
Jin, Wen ;
Sun, Yifei ;
Xu, Yuemei ;
Wang, Yipin ;
Liang, Xiubin ;
Su, Dongming .
MOLECULAR CANCER, 2021, 20 (01)