CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling

Journal of Biomedical Science

Xiaochun Wang¹  Fang Wang²  Pengwei Lv²  Jingruo Li²  Mingli Han²  Lin Li²  Zhuo Chen²  Yuanting Gu²  Lingling Dong²  Nan Wang² 

[1] Department of Breast Surgery, Affiliated Hospital of Hebei University, 071000, Baoding, China;Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Erqi, 450000, Zhengzhou, China;

关键词: Breast cancer;    Circular RNA;    circNOL10;    miR-767-5p;    SOCS2;    JAK/STAT signaling;   

DOI  :  10.1186/s12929-020-00697-0

来源: Springer

【 摘 要 】

BackgroundCircular RNAs (circRNAs) have caught increasing attentions and interests for their important involvement in cancer initiation and progression. This study aims to investigate the biological functions of circNOL10 and its potential molecular mechanisms in breast cancer (BC).Materials and methodsqRT-PCR and western blot assays were performed to measure the expression of related genes. CCK-8, colony formation, flow cytomerty and transwell assays were used to assess cell proliferation, cell cycle, migration and invasion. RNA pull-down, luciferase reporter and RIP assays were applied to address the potential regulatory mechanism of circNOL10.ResultsCircNOL10 was down-regulated in BC tissues and cells. Low expression of circNOL10 was associated with larger tumor size, advanced TNM stage, lymph node metastasis and unfavorable prognosis. Overexpression of circNOL10 inhibited cell proliferation, migration, invasion and EMT in vitro and slowed xenograft tumor growth in vivo. Mechanistically, circNOL10 could act as a molecular sponge for miR-767-5p, leading to the up-regulation of suppressors of cytokine signaling 2 (SOCS2) and inactivation of JAK2/STAT5 pathway. Moreover, circNOL10-mediated suppression of malignant phenotypes was attenuated by miR-767-5p. Similar to circNOL10, enforced expression of SOCS2 also resulted in the suppression of cell proliferation and metastasis. Furthermore, knockdown of SOCS2 reversed the tumor-suppressive effect induced by circNOL10.ConclusionsCircNOL10 repressed BC development via inactivation of JAK2/STAT5 signaling by regulating miR-767-5p/SOCS2 axis. Our findings offer the possibility of exploiting circNOL10 as a therapeutic and prognostic target for BC patients.

【 授权许可】

CC BY