CircRNA circRREB1 promotes tumorigenesis and progression of breast cancer by activating Erk1/2 signaling through interacting with GNB4

作者全名：Chen, Hong; Wang, Xiaosong; Cheng, Hang; Deng, Yumei; Chen, Junxia; Wang, Bin

作者地址：[Chen, Hong; Wang, Xiaosong; Cheng, Hang; Deng, Yumei; Chen, Junxia] Chongqing Med Univ, Dept Cell Biol & Genet, Chongqing 400016, Peoples R China; [Wang, Bin] Chongqing Univ Technol, Affiliated Cent Hosp, Peoples Hosp Chongqing 7, Dept Oncol, Chongqing 400054, Peoples R China

通信作者：Wang, B (通讯作者)，Chongqing Univ Technol, Affiliated Cent Hosp, Peoples Hosp Chongqing 7, Dept Oncol, Chongqing 400054, Peoples R China.

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001226249900001

JCR分区：Q1

影响因子：3.4

年份：2024

卷号：10

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：CircRREB1; RNA -Binding protein; GNB4; Erk1/2 signaling; Breast cancer

摘要：Current investigations have illuminated the essential roles played by circular RNAs (circRNAs) in driving breast cancer (BC) tumorigenesis. However, the functional implications and molecular underpinnings of most circRNAs in BC are not well characterized. Here, Circular RNA (circRNA) expression profiles were analyzed in four surgically resected BC cases along with adjacent noncancerous tissues applying RNA microarray analysis. The levels and prognostic implications of circRREB1 in BC were subjected to quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Experimental manipulation of circRREB1 levels in both in vivo and in vitro settings further delineated its role in BC cell growth, invasion, and metastasis. The mechanical verification of circRREB1's interaction with GNB4 was established through RNA pull-down, mass spectrometry, Western blot analysis, RNA immunoprecipitation assays (RIP), fluorescence ISH (FISH), and rescue experiments. We found that circRREB1 exhibited significant upregulation in BC tissues and cells, implicating its association with an unfavorable prognosis in BC patients. CircRREB1 knockdown elicited anti-proliferative, anti-migratory, anti-invasive, and pro-apoptotic effects in BC cells, whereas its upregulation exerted opposing influences. Follow-up mechanistic examinations suggested that circRREB1 might interact with GNB4 directly, inducing the activation of Erk1/2 signaling and driving BC progression. Our findings collectively indicate that the interplay of circRREB1 with GNB4 promotes Erk1/2 signaling, thereby fostering BC progression, and positioning circRREB1 as a candidate therapeutic target for intervention in BC.

基金机构：National Natural Science Foundation of China [82173170]

基金资助正文：Funding statement This work was supported by grants from the National Natural Science Foundation of China (82173170) .