Dataset Information

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.

SUBMITTER: Wang F

PROVIDER: S-EPMC7780627 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Circular RNAs (circRNAs) are a new class of single-stranded RNAs that form a continuous loop with crucial role in regulation of gene expression. Because their circular conformation conforms numerous properties, circRNAs have been investigated recently to demonstrate their important role in the development and progression of various cancers. However, the function of circRNAs and their regulatory outcomes in cervical cancer (CC) have rarely been explored. In this study, the role and molecular mechanism of hsa_circ_0107593 in cervical cancer are demonstrated. Quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of hsa_circ_0107593 and three miRNAs (hsa-miR-20a-5p, 93-5p, and 106b-5p) in paired CC tissues (tumor tissue vs. adjacent normal cervical tissue), CC cell lines, and human normal cervical epithelial immortalized cell line. A series of functional experiments were conducted to assess the function of hsa_circ_0107593 in CC development. The Receiver Operating Characteristic (ROC) curve was plotted to estimate the diagnostic value of hsa_circ_0107593 in CC. The dual-luciferase reporter assay was used to explore the interaction between hsa_circ_0107593 and hsa-miR-20a-5p/93-5p/106b-5p. Bioinformatic analysis was conducted to predict the target mRNAs, pathways, and functional enrichment. The results revealed that hsa_circ_0107593 has low expression in CC tissues and CC cell lines. Moreover, negative correlations of hsa_circ_0107593 expression were found against tumor diameter, FIGO stage, and myometrial invasion. Also, hsa_circ_0107593 impedes CC cell proliferation, migration, and invasion. Based on ROC curve analysis, hsa_circ_0107593 could serve as a diagnostic biomarker. Its low expression may indicate increased patient's risk to developing cervical cancer. Mechanistically, hsa_circ_0107593 serves as a sponge of hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p. Collectively, our study implies that hsa_circ_0107593 has tumor-suppressing activity in CC by physically binding with hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p.