The circACTN4 interacts with FUBP1 to promote tumorigenesis and progression of breast cancer by regulating the expression of proto-oncogene MYC

作者全名："Wang, Xiaosong; Xing, Lei; Yang, Rui; Chen, Hang; Wang, Min; Jiang, Rong; Zhang, Luyu; Chen, Junxia"

作者地址："[Wang, Xiaosong; Yang, Rui; Chen, Hang; Wang, Min; Chen, Junxia] Chongqing Med Univ, Dept Cell Biol & Genet, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Xing, Lei] Chongqing Med Univ, Dept Endocrine & Breast Surg, Affiliated Hosp 1, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Jiang, Rong] Chongqing Med Univ, Lab Stem Cells & Tissue Engn, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Zhang, Luyu] Chongqing Med Univ, Mol Med & Canc Res Ctr, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Chen, JX (corresponding author), Chongqing Med Univ, Dept Cell Biol & Genet, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：MOLECULAR CANCER

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000663026200005

JCR分区：Q1

影响因子：37.3

年份：2021

卷号：20

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：circactn4; FUBP1; The RNA-binding protein; MYC; Breast cancer

摘要："Background Recent studies have revealed that circular RNAs (circRNAs) play significant roles in the occurrence and development of many kinds of cancers including breast cancer (BC). However, the potential functions of most circRNAs and the molecular mechanisms underlying progression of BC remain elusive. Method Here, Circular RNA microarray was executed in 4 pairs of breast cancer tissues and para-cancer tissues. The expression and prognostic significance of circACTN4 in BC cells and tissues were determined by qRT-PCR and in situ hybridization. Gain-and loss-of-function experiments were implemented to observe the impacts of circACTN4 on the growth, invasion, and metastasis of BC cells in vitro and in vivo. Mechanistically, chromatin immunoprecipitation, luciferase reporter, RNA pulldown, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization and co-immunoprecipitation assays were executed. Results CircACTN4 was significantly upregulated in breast cancer tissues and cells, its expression was correlated with clinical stage and poor prognosis of patients with BC. Ectopic expression of circACTN4 strikingly facilitated the growth, invasion, and metastasis of breast cancer cells in vitro and in vivo. Whereas knockdown of circACTN4 revealed opposite roles. CircACTN4 was mainly distributed in the nucleus. Further mechanistic research proved that circACTN4 could competitively bind to far upstream element binding protein 1 (FUBP1) to prevent the combination between FUBP1 and FIR, thereby activating MYC transcription and facilitating tumor progression of breast cancer. Furthermore, we found that upstream transcription factor 2 (USF2) might promote the biogenesis of circACTN4. Conclusion Our findings uncover a pivotal mechanism that circACTN4 mediated by USF2 might interact with FUBP1 to promote the occurrence and development of breast cancer via enhancing the expression of MYC. CircACTN4 could be a novel potential target for diagnosis and treatment of breast cancer."

基金机构：National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672536]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJZD-K202000405]; Innovation research group in Colleges and Universities Program of Chongqing Municipal Education Commission [CXQT20012]; project of the top-notch talent cultivation program for the graduate students of Chongqing Medical University [BJRC201918]

基金资助正文："This work was supported by National Natural Science Foundation of China (No. 81672536), Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJZD-K202000405), Innovation research group in Colleges and Universities Program of Chongqing Municipal Education Commission (No. CXQT20012) and the project of the top-notch talent cultivation program for the graduate students of Chongqing Medical University (No. BJRC201918)."