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

Abstract

BACKGROUND:

Circular 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 METHODS:

qRT-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.

RESULTS:

CircNOL10 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.

CONCLUSIONS:

CircNOL10 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.

• Authors: Fang Wang, Xiaochun Wang, Jingruo Li, Pengwei Lv, Mingli Han, Lin Li, Zhuo Chen, Lingling Dong, Nan Wang, Yuanting Gu
• Journal: Journal of biomedical science (J Biomed Sci) Vol. 28 Issue 1 Pg. 4 (Jan 04 2021) ISSN: 1423-0127 [Electronic] England
• PMID: 33397365 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• MIRN-767 microRNA, human
• MicroRNAs
• RNA, Circular

Topics

• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (diet therapy)
• Cell Line, Tumor
• Disease Progression
• Female
• Humans
• MicroRNAs (metabolism)
• RNA, Circular (pharmacology)
• Signal Transduction (drug effects)