CircMAN1A2 promotes vasculogenic mimicry of nasopharyngeal carcinoma cells through upregulating ERBB2 via sponging miR-940

被引:7
作者
Mo, Huaqing [1 ]
Shen, Jingyi [1 ]
Zhong, Yuxiao [1 ]
Chen, Zenan [1 ]
Wu, Tong [1 ]
Lv, Yanyu [1 ]
Xie, Yanyan [1 ]
Hao, Yanrong [1 ]
机构
[1] Guangxi Acad Med Sci, Peoples Hosp Guangxi Zhuang Autonomous Reg, Canc Ctr, Nanning 530021, Peoples R China
基金
中国国家自然科学基金;
关键词
MiR-940; ERBB2; Vasculogenic mimicry; Nasopharyngeal carcinoma; PI3K; AKT; mTOR signaling pathway; CIRCULAR RNAS; EXPRESSION; GROWTH; PROGNOSIS; ROLES; HER2;
D O I
10.32604/or.2022.027534
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Nasopharyngeal carcinoma (NPC) is the most prevalent human primary malignancy of the head and neck, and the presence of vasculogenic mimicry (VM) renders anti-angiogenic therapy ineffective and poorly prognostic. However, the underlying mechanisms are unclear. In the present study, we used miR-940 silencing and overexpression for in vitro NPC cell EdU staining, wound healing assay and 3D cell culture assay, and in vivo xenograft mouse model and VM formation to assess miR-940 function. We found that ectopic miR-940 expression reduced NPC cell proliferation, migration and VM, as well as tumorigenesis in vivo. By bioinformatic analysis, circMAN1A2 was identified as a circRNA that binds to miR-940. Mechanistically, we confirmed that circMAN1A2 acts as a sponge for miR-940, impairs the inhibitory effect of miR-940 on target ERBB2, and then activates the PI3K/AKT/mTOR signaling pathway using RNA-FISH, dual luciferase reporter gene and rescue analysis assays. In addition, upregulation of ERBB2 expression is associated with clinical staging and poor prognosis of NPC. Taken together, the present findings suggest that circMAN1A2 promotes VM formation and progression of NPC through miR-940/ERBB2 axis and further activates the PI3K/AKT/mTOR pathway. Therefore, circMAN1A2 may become a biomarker and therapeutic target for anti-angiogenic therapy in patients with nasopharyngeal carcinoma.
引用
收藏
页码:187 / 199
页数:13
相关论文
共 52 条
[1]   Oncogenic Roles of the PI3K/AKT/mTOR Axis [J].
Aoki, Masahiro ;
Fujishita, Teruaki .
VIRUSES, GENES, AND CANCER, 2017, 407 :153-189
[2]   Emerging therapeutic targets for nasopharyngeal carcinoma: opportunities and challenges [J].
Baloche, Valentin ;
Ferrand, Francois-Regis ;
Makowska, Anna ;
Even, Caroline ;
Kontny, Udo ;
Busson, Pierre .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2020, 24 (06) :545-558
[3]   Identification and validation of novel ERBB2 (HER2, NEU) targets including genes involved in angiogenesis [J].
Beckers, J ;
Herrmann, F ;
Rieger, S ;
Drobyshev, AL ;
Horsch, M ;
de Angelis, MH ;
Seliger, B .
INTERNATIONAL JOURNAL OF CANCER, 2005, 114 (04) :590-597
[4]   Long-term efficacy and adverse reactions of IMRT combined with Endostar versus IMRT combined with chemotherapy for locally advanced nasopharyngeal carcinoma: a retrospective study [J].
Chen, Wei ;
Wang, Fangfang ;
Yang, Zhendong ;
Zhang, Tingting ;
Shen, Mingjun ;
Wang, Rensheng ;
Kang, Min .
ANNALS OF PALLIATIVE MEDICINE, 2021, 10 (11) :11891-11900
[5]   Antisense technology: A review [J].
Crooke, Stanley T. ;
Liang, Xue-Hai ;
Baker, Brenda F. ;
Crooke, Rosanne M. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2021, 296
[6]   Therapeutic strategies for Huntington's disease [J].
Estevez-Fraga, Carlos ;
Flower, Michael D. ;
Tabrizi, Sarah J. .
CURRENT OPINION IN NEUROLOGY, 2020, 33 (04) :508-518
[7]   The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC [J].
Fabian, Marc R. ;
Sonenberg, Nahum .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2012, 19 (06) :586-593
[8]   circMAN1A2 could serve as a novel serum biomarker for malignant tumors [J].
Fan, Chun-Mei ;
Wang, Jin-Peng ;
Tang, Yan-Yan ;
Zhao, Jin ;
He, Shu-Yi ;
Xiong, Fang ;
Guo, Can ;
Xiang, Bo ;
Zhou, Ming ;
Li, Xiao-Ling ;
Li, Yong ;
Li, Gui-Yuan ;
Xiong, Wei ;
Zeng, Zhao-Yang .
CANCER SCIENCE, 2019, 110 (07) :2180-2188
[9]   Vascular mimicry: changing the therapeutic paradigms in cancer [J].
Fathi Maroufi, Nazila ;
Taefehshokr, Sina ;
Rashidi, Mohammad-Reza ;
Taefehshokr, Nima ;
Khoshakhlagh, Mahdieh ;
Isazadeh, Alireza ;
Mokarizadeh, Narmin ;
Baradaran, Behzad ;
Nouri, Mohammad .
MOLECULAR BIOLOGY REPORTS, 2020, 47 (06) :4749-4765
[10]   circRNA mannosidase alpha class 1A member 2 contributes to the proliferation and motility of papillary thyroid cancer cells through upregulating metadherin via absorbing microRNA-449a [J].
Feng, Yao ;
Yang, Xinxin ;
Wang, Yibo ;
Chi, Nannan ;
Yu, Jianan ;
Fu, Xiandong .
ANTI-CANCER DRUGS, 2023, 34 (01) :44-56