circ_0008285 Regulates Glioma Progression via the miR-384/HMGB1 Axis

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Abstract

Background

Recent studies indicate that circular RNAs (circRNAs) have been implicated in the initiation or progression of a wide spectrum of diseases. In the current study, we explored the potential engagement of circ_0008285 in glioma and investigated the downstream regulators.

Methods

The detection of circ_0008285 level in glioma specimens and cell lines was conducted by quantitative real-time polymerase chain reaction. The chi-squared test was employed to evaluate the relationship between the circ_0008285 level and the clinical features of glioma patients. The roles of circ_0008285 on the proliferation and apoptosis of glioma cells were studied by knockdown experiment. Meanwhile, the regulatory relationship of circ_0008285, miR-384, and high mobility group protein B1 (HMGB1) was explored in glioma cells, and we explored the effects of circ_0008285/miR-384/HMGB1 pathway on glioma cells.

Results

In glioma specimens and cell lines, the expression of circ_0008285 was significantly increased, and a high circ_0008285 level was associated with a larger tumor size and more advanced grading in glioma patients. Furthermore, downregulating circ_0008285 suppressed proliferation and triggered apoptosis of glioma cells, which was associated with a cell cycle arrest at the G1/G0 phase. Mechanism studies indicated that circ_0008285 regulated HMGB1 by sponging miR-384. Functional experiments demonstrated that circ_0008285 promoted the malignant phenotype of glioma cells by miR-384/HMGB1 axis.

Conclusion

Our study revealed circ_0008285 as a novel oncogenic factor in glioma through modulating the miR-384/HMGB1 pathway, suggesting that targeting circ_0008285 could serve as a strategy for glioma management.

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Most cited references 37

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Natural RNA circles function as efficient microRNA sponges.

Thomas B. Hansen, Trine I. Jensen, Bettina H. Clausen … (2013)

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.

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Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis

Yibing Yang, Xinya Gao, Maolei Zhang … (2017)

Abstract Background Circular RNAs (circRNAs) are RNA transcripts that are widespread in the eukaryotic genome. Recent evidence indicates that circRNAs play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported. Methods CircRNA deep sequencing was performed by using 10 pathologically diagnosed glioblastoma samples and their paired adjacent normal brain tissues. Northern blotting, Sanger sequencing, antibody, and liquid chromatograph Tandem Mass Spectrometer were used to confirm the existence of circ-FBXW7 and its encoded protein in in two cell lines. Lentivirus-transfected stable U251 and U373 cells were used to assess the biological functions of the novel protein in vitro and in vivo (five mice per group). Clinical implications of circ-FBXW7 were assessed in 38 pathologically diagnosed glioblastoma samples and their paired periphery normal brain tissues by using quantitative polymerase chain reaction (two-sided log-rank test). Results Circ-FBXW7 is abundantly expressed in the normal human brain (reads per kilobase per million mapped reads [RPKM] = 9.31). The spanning junction open reading frame in circ-FBXW7 driven by internal ribosome entry site encodes a novel 21-kDa protein, which we termed FBXW7-185aa. Upregulation of FBXW7-185aa in cancer cells inhibited proliferation and cell cycle acceleration, while knockdown of FBXW7-185aa promoted malignant phenotypes in vitro and in vivo. FBXW7-185aa reduced the half-life of c-Myc by antagonizing USP28-induced c-Myc stabilization. Moreover, circ-FBXW7 and FBXW7-185aa levels were reduced in glioblastoma clinical samples compared with their paired tumor-adjacent tissues (P < .001). Circ-FBXW7 expression positively associated with glioblastoma patient overall survival (P = .03). Conclusions Endogenous circRNA encodes a functional protein in human cells, and circ-FBXW7 and FBXW7-185aa have potential prognostic implications in brain cancer.

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Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis.

Timothy Brown, Matthew Brennan, Michael CH Li … (2016)

Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies.

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Author and article information

Contributors

Changjiang Lei:

ORCID: https://orcid.org/0000-0002-6830-0419

Yamei Liu:

ORCID: https://orcid.org/0000-0003-3848-1420

Journal

Journal ID (nlm-ta): Int J Genomics

Journal ID (iso-abbrev): Int J Genomics

Journal ID (publisher-id): IJG

Title: International Journal of Genomics

Publisher: Hindawi

ISSN (Print): 2314-436X

ISSN (Electronic): 2314-4378

Publication date Collection: 2023

Publication date (Electronic): 3 August 2023

Volume: 2023

Electronic Location Identifier: 1680634

Affiliations

¹Department of Internal Medicine, The Fifth Hospital of Wuhan, Wuhan 430050, China

²Department of Internal Medicine, Wuhan Hospital of China University of Geoscience, Wuhan 430074, China

³Department of Surgery, The Fifth Hospital of Wuhan, Wuhan, Hubei 430050, China

⁴Qilu Cell Therapy Technology Co., Ltd., Jinan 250100, China

⁵Department of Oncology, The Fifth Hospital of Wuhan, Wuhan 430050, China

⁶National Research Center of Engineering and Technology for Veterinary Biologicals/Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China

⁷Jiangsu Co-Innovation Center for Prevention and Control of Important Animal, Infectious Diseases and Zoonoses, Yangzhou 225009, China

⁸GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou 225321, China

Author notes

Academic Editor: Ferenc Olasz

Author information

Manli Yan https://orcid.org/0009-0005-2798-4323

Caihong Hu https://orcid.org/0000-0001-8994-3782

Qi Hu https://orcid.org/0000-0003-1759-1102

Heran Ma https://orcid.org/0000-0002-7525-3008

Changjiang Lei https://orcid.org/0000-0002-6830-0419

Yamei Liu https://orcid.org/0000-0003-3848-1420

Article

DOI: 10.1155/2023/1680634

PMC ID: 10415084

SO-VID: cf32d6a7-5f7d-4991-be6d-d3be5ff58d69

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 28 September 2022

Date revision received : 6 July 2023

Date accepted : 12 July 2023

Funding

Funded by: Wuhan Municipal Health Commission

Award ID: WJ2023M135