<i>circ-hnRNPU</i> inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Recent evidence reveals the emerging functions of circular RNA (circRNA) and protein glycosylation in cancer progression. However, the roles of circRNA in regulating glycosyltransferase expression in gastric cancer remain to be determined.

Methods

Circular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by chromatin immunoprecipitation, RNA immunoprecipitation, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA and its partners on the glycosylation, growth, invasion, and metastasis of gastric cancer cells.

Results

Circ-hnRNPU, an exonic circRNA derived from heterogenous nuclear ribonuclear protein U ( hnRNPU), was identified to exert tumor suppressive roles in protein glycosylation and progression of gastric cancer. Mechanistically, circ-hnRNPU physically interacted with non-POU domain containing octamer binding (NONO) protein to induce its cytoplasmic retention, resulting in down-regulation of glycosyltransferases ( GALNT2, GALNT6, MGAT1) and parental gene hnRNPU via repression of nuclear NONO-mediated c-Myc transactivation or cytoplasmic NONO-facilitated mRNA stability. Rescue studies indicated that circ-hnRNPU inhibited the N- and O-glycosylation, growth, invasion, and metastasis of gastric cancer cells via interacting with NONO protein. Pre-clinically, administration of lentivirus carrying circ-hnRNPU suppressed the protein glycosylation, tumorigenesis, and aggressiveness of gastric cancer xenografts. In clinical cases, low circ-hnRNPU levels and high NONO or c-Myc expression were associated with poor survival outcome of gastric cancer patients.

Conclusions

These findings indicate that circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13046-023-02898-5.

Related collections

Most cited references 55

Record: found
Abstract: found
Article: not found

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)

This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.

0 comments Cited 27635 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Natural RNA circles function as efficient microRNA sponges.

Thomas B. Hansen, Trine I. Jensen, Bettina H. Clausen … (2014)

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.

0 comments Cited 2178 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The biogenesis, biology and characterization of circular RNAs

Lasse S. Kristensen, Maria Andersen, Lotte V. W. Stagsted … (2019)

Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules in eukaryotes with tissue-specific and cell-specific expression patterns, whose biogenesis is regulated by specific cis-acting elements and trans-acting factors. Some circRNAs are abundant and evolutionarily conserved, and many circRNAs exert important biological functions by acting as microRNA or protein inhibitors ('sponges'), by regulating protein function or by being translated themselves. Furthermore, circRNAs have been implicated in diseases such as diabetes mellitus, neurological disorders, cardiovascular diseases and cancer. Although the circular nature of these transcripts makes their detection, quantification and functional characterization challenging, recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.

0 comments Cited 1775 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Qiangsong Tong: qs_tong@hotmail.com

Liduan Zheng: ld_zheng@hotmail.com

Journal

Journal ID (nlm-ta): J Exp Clin Cancer Res

Journal ID (iso-abbrev): J Exp Clin Cancer Res

Title: Journal of Experimental & Clinical Cancer Research : CR

Publisher: BioMed Central (London )

ISSN (Print): 0392-9078

ISSN (Electronic): 1756-9966

Publication date (Electronic): 23 November 2023

Publication date PMC-release: 23 November 2023

Publication date Collection: 2023

Volume: 42

Electronic Location Identifier: 313

Affiliations

[1 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Pathology, Union Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; 1277 Jiefang Avenue, Wuhan, Hubei Province 430022 P. R. China

[2 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Pediatric Surgery, Union Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; 1277 Jiefang Avenue, Wuhan, Hubei Province 430022 P. R. China

[3 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Geriatrics, Union Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; 1277 Jiefang Avenue, Wuhan, Hubei Province 430022 P. R. China

Article

Publisher ID: 2898

DOI: 10.1186/s13046-023-02898-5

PMC ID: 10666356

PubMed ID: 37993881

SO-VID: deacbab4-cf40-4bf3-9b0f-8746ae3b391f

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 28 July 2023

Date accepted : 12 November 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81903008

Award ID: 82072801

Award ID: 82173316

Award ID: 82293663

Award Recipient : Qiangsong Tong

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: gastric cancer,circular rna,heterogenous nuclear ribonuclear protein u,non-pou domain containing octamer binding,glycosylation

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: gastric cancer, circular rna, heterogenous nuclear ribonuclear protein u, non-pou domain containing octamer binding, glycosylation

circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression

Read this article at

Abstract

Background

Methods

Results

Conclusions

Supplementary Information

Related collections

Karger: Oncology

Most cited references 55

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Natural RNA circles function as efficient microRNA sponges.

The biogenesis, biology and characterization of circular RNAs

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 438

Cited by 3