Circular RNA hsa_circ_0072309 inhibits proliferation and invasion of breast cancer cells via targeting miR-492

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Abstract

Background

Although the number of circular RNAs (circRNAs) that has been identified in multiple cancer tissues continues to increase, the relationship between circRNA expression and carcinogenesis remains unknown. The role of hsa_circ_0072309 in breast cancer has remained undefined until now. In this study, we aimed to investigate the role of hsa_circ_0072309 in breast cancer progression.

Methods

hsa_circ_0072309 expression in breast cancer tissues was analyzed using qRT-PCR. A series of functional experiments were carried out to investigate hsa_circ_0072309 function in breast cancer development and its underlying molecular mechanisms.

Results

hsa_circ_0072309 expression in breast cancer tissues was upregulated relative to that in adjacent normal tissues. hsa_circ_0072309 could serve as a prognostic biomarker of breast cancer. hsa_circ_0072309 overexpression dramatically inhibited the proliferation, migration, and invasion of breast cancer cells in vitro. In vivo assays revealed that the ectopic expression of hsa_circ_0072309 repressed breast cancer growth. The results of our mechanistic studies indicated that hsa_circ_0072309 could act as the sponge of miR-492, which exhibited increased expression in breast cancer tissues. Hsa_circ_0072309 suppressed breast cancer cell proliferation, migration, and invasion by inhibiting miR-492.

Conclusion

Our findings revealed for the first time that the hsa_circ_0072309-miR-492 axis plays an essential role in breast cancer progression.

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Most cited references 9

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MicroRNA sequence and expression analysis in breast tumors by deep sequencing.

T Farazi, H M Horlings, J. ten Hoeve … (2011)

MicroRNAs (miRNA) regulate many genes critical for tumorigenesis. We profiled miRNAs from 11 normal breast tissues, 17 noninvasive, 151 invasive breast carcinomas, and 6 cell lines by in-house-developed barcoded Solexa sequencing. miRNAs were organized in genomic clusters representing promoter-controlled miRNA expression and sequence families representing seed sequence-dependent miRNA target regulation. Unsupervised clustering of samples by miRNA sequence families best reflected the clustering based on mRNA expression available for this sample set. Clustering and comparative analysis of miRNA read frequencies showed that normal breast samples were separated from most noninvasive ductal carcinoma in situ and invasive carcinomas by increased miR-21 (the most abundant miRNA in carcinomas) and multiple decreased miRNA families (including miR-98/let-7), with most miRNA changes apparent already in the noninvasive carcinomas. In addition, patients that went on to develop metastasis showed increased expression of mir-423, and triple-negative breast carcinomas were most distinct from other tumor subtypes due to upregulation of the mir~17-92 cluster. However, absolute miRNA levels between normal breast and carcinomas did not reveal any significant differences. We also discovered two polymorphic nucleotide variations among the more abundant miRNAs miR-181a (T19G) and miR-185 (T16G), but we did not identify nucleotide variations expected for classical tumor suppressor function associated with miRNAs. The differentiation of tumor subtypes and prediction of metastasis based on miRNA levels is statistically possible but is not driven by deregulation of abundant miRNAs, implicating far fewer miRNAs in tumorigenic processes than previously suggested. ©2011 AACR.

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Comprehensive profile of differentially expressed circular RNAs reveals that hsa_circ_0000069 is upregulated and promotes cell proliferation, migration, and invasion in colorectal cancer

Jia‐ni Guo, Jin Li, Chang-li Zhu … (2016)

Background Nowadays, despite great progress in cancer research, the detailed mechanisms of colorectal cancer (CRC) are still poorly understood. Circular RNAs (circRNAs), a new star of the non-coding RNA network, have been identified as critical regulators in various cancers, including CRC. Methods and results In this study, by using unsupervised hierarchical clustering analysis, a novel dysregulated circRNA, hsa_circ_0000069, was found. The expression of hsa_circ_0000069 was measured in 30 paired CRC tissues and adjacent noncancerous tissues using quantitative polymerase chain reaction. A high expression of hsa_circ_0000069 was observed in CRC tissues and correlated with patients’ age and tumor, node, metastasis (TNM) stage (P<0.05). Furthermore, by using specifically designed siRNAs in CRC cells, a functional analysis was performed which revealed that hsa_circ_0000069 knockdown could notably inhibit cell proliferation, migration, and invasion, and induce G0/G1 phase arrest of cell cycle in vitro. Conclusion This study’s findings are the first to demonstrate that hsa_circ_0000069, an important regulator in cancer progression, could be a promising target in the diagnosis and therapy in colorectal cancer.

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CiRS‐7 targeting miR‐7 modulates the progression of non‐small cell lung cancer in a manner dependent on NF‐κB signalling

Chongyu Su, Yi Han, Hongtao Zhang … (2018)

Abstract The purpose of this study was to figure out the effect of ciRS‐7/miR‐7/NF‐κB axis on the development of non‐small cell lung cancer (NSCLC). In response, the expressions of ciRS‐7, miR‐7 and NF‐κB subunit (ie RELA) within NSCLC tissues and cell lines were determined with real‐time polymerase chain reaction (RT‐PCR) and Western blot. Moreover, the NSCLC cells were transfected with pcDNA3‐ciRS‐7‐ir, pcDNA3‐ciRS‐7, miR‐NC and miR‐7 mimic. Furthermore, the targeted relationships between ciRS‐7 and miR‐7, as well as between miR‐7 and RELA, were confirmed by luciferase reporter assay. The proliferation, migration and apoptosis of NSCLC cells were, successively, measured using CCK‐8 assay, wound‐healing assay and flow cytometry test. Consequently, ciRS‐7, miR‐7, histopathological grade, lymph node metastasis and histopathological stage could independently predict the prognosis of patients with NSCLC (all P < .05). Moreover, remarkably up‐regulated ciRS‐7 and RELA expressions, as along with down‐regulated miR‐7 expressions, were found within NSCLC tissues and cells in comparison with normal ones (P < .05). Besides, overexpressed ciRS‐7 and underexpressed miR‐7 were correlated with increased proliferation, migration and invasion, yet reduced apoptosis rate of NSCLC cells (P < .05). More than that, ciRS‐7 specifically targeted miR‐7 to reduce its expressions (P < .05). Ultimately, the NSCLC cells within miR‐7 + RELA group were observed with superior proliferative, migratory and invasive capabilities than those within miR‐7 group (P < .05), and RELA expression was also significantly modified by both ciRS‐7 and miR‐7 (P < .05). In conclusion, the ciRS‐7/miR‐7/NF‐kB axis could exert pronounced impacts on the proliferation, migration, invasion and apoptosis of NSCLC cells.

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Author and article information

Journal

Journal ID (nlm-ta): Cancer Manag Res

Journal ID (iso-abbrev): Cancer Manag Res

Journal ID (publisher-id): Cancer Management and Research

Title: Cancer Management and Research

Publisher: Dove Medical Press

ISSN (Electronic): 1179-1322

Publication date Collection: 2019

Publication date (Electronic): 22 January 2019

Volume: 11

Pages: 1033-1041

Affiliations

[1 ]Department of Breast Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China

[2 ]Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China, huawangh@ 123456163.com

Author notes

Correspondence: Hua Wang, Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, No.32, Dajian Lane, Lucheng District, Wenzhou 325000, China, Email huawangh@ 123456163.com

Article

Publisher ID: cmar-11-1033

DOI: 10.2147/CMAR.S186857

PMC ID: 6349082

PubMed ID: 30774431

SO-VID: 35fb90d0-ee0d-4e30-a4eb-0c4cf3695b64

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The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

Circular RNA hsa_circ_0072309 inhibits proliferation and invasion of breast cancer cells via targeting miR-492

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Abstract

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Karger: Oncology

Most cited references 9

MicroRNA sequence and expression analysis in breast tumors by deep sequencing.

Comprehensive profile of differentially expressed circular RNAs reveals that hsa_circ_0000069 is upregulated and promotes cell proliferation, migration, and invasion in colorectal cancer

CiRS‐7 targeting miR‐7 modulates the progression of non‐small cell lung cancer in a manner dependent on NF‐κB signalling

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