N6-methyladenosine-modified oncofetal lncRNA MIR4435-2HG contributed to stemness features of hepatocellular carcinoma cells by regulating rRNA 2′-O methylation

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

The unique expression pattern endows oncofetal genes with great value in cancer diagnosis and treatment. However, only a few oncofetal genes are available for clinical use and the underlying mechanisms that drives the fetal-like reprogramming of cancer cells remain largely unknown.

Methods

Microarray assays and bioinformatic analyses were employed to screen for potential oncofetal long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). The expression levels of MIR4435-2HG, NOP58 ribonucleoprotein (NOP58), insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) and stem markers were detected by quantitative polymerase chain reaction. The 2′-O-methylation (2′-O-Me) status of rRNA were detected through reverse transcription at low dNTP concentrations followed by PCR. The regulation of MIR4435-2HG by IGF2BP1 was explored by RNA immunoprecipitation (RIP), methylated RIP (MeRIP) and dual-luciferase assays. The interaction between MIR4435-2HG and NOP58 was investigated by RNA Pulldown, RIP and protein stability assays. In vitro and in vivo function assays were performed to detect the roles of MIR4435-2HG/NOP58 in HCC.

Results

MIR4435-2HG was an oncofetal lncRNA associated with poor prognosis in HCC. Functional experiments showed that overexpression of MIR4435-2HG remarkably enhanced the stem-cell properties of HCC cells, promoting tumorigenesis in vitro and in vivo. Mechanically, MIR4435-2HG directly bound NOP58 and IGF2BP1. IGF2BP1 upregulated MIR4435-2HG expression in HCC through N6-methyladenosine (m6A) modification. Moreover, MIR4435-2HG protected NOP58 from degradation, which raised rRNA 2’-O-Me levels and promoted internal ribosome entry site (IRES)-dependent translation of oncogenes.

Conclusions

This study identified an oncofetal lncRNA MIR4435-2HG, characterized the role of MIR4435-2HG/NOP58 in stemness maintenance and proliferation of HCC cells, and confirmed m6A as a ‘driver’ that reactivated MR4435-2HG expression in HCC.

Supplementary Information

The online version contains supplementary material available at 10.1186/s11658-023-00493-2.

Related collections

Most cited references 37

Record: found
Abstract: found
Article: not found

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

0 comments Cited 31886 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses

Zefang Tang, Chenwei Li, Boxi Kang … (2017)

Abstract Tremendous amount of RNA sequencing data have been produced by large consortium projects such as TCGA and GTEx, creating new opportunities for data mining and deeper understanding of gene functions. While certain existing web servers are valuable and widely used, many expression analysis functions needed by experimental biologists are still not adequately addressed by these tools. We introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based tool to deliver fast and customizable functionalities based on TCGA and GTEx data. GEPIA provides key interactive and customizable functions including differential expression analysis, profiling plotting, correlation analysis, patient survival analysis, similar gene detection and dimensionality reduction analysis. The comprehensive expression analyses with simple clicking through GEPIA greatly facilitate data mining in wide research areas, scientific discussion and the therapeutic discovery process. GEPIA fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources. GEPIA is available at http://gepia.cancer-pku.cn/.

0 comments Cited 3726 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Functional Classification and Experimental Dissection of Long Noncoding RNAs

Florian Kopp, Joshua Mendell (2018)

Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of DNA regulatory elements, such as enhancers and promoters, regularly initiate bidirectional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the lncRNA field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating lncRNA function. We categorize lncRNA loci into those that regulate gene expression in cis versus those that perform functions in trans , and propose an experimental approach to dissect lncRNA activity based on these classifications. These strategies to further understand lncRNAs promise to reveal new and unanticipated biology, with great potential to advance our understanding of normal physiology and disease.

0 comments Cited 1312 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Jinfeng Huang: jfhuang@smmu.edu.cn

Zhiyong Liu: chyang@sibs.ac.cn

Fang Wang: wfsjz@smmu.edu.cn

Journal

Journal ID (nlm-ta): Cell Mol Biol Lett

Journal ID (iso-abbrev): Cell Mol Biol Lett

Title: Cellular & Molecular Biology Letters

Publisher: BioMed Central (London )

ISSN (Print): 1425-8153

ISSN (Electronic): 1689-1392

Publication date (Electronic): 27 October 2023

Publication date PMC-release: 27 October 2023

Publication date Collection: 2023

Volume: 28

Electronic Location Identifier: 89

Affiliations

[1 ]GRID grid.73113.37, ISNI 0000 0004 0369 1660, Department of Medical Genetics, , Naval Medical University, ; Shanghai, 200433 China

[2 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Assisted Reproduction, , Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, ; Shanghai, 200011 China

[3 ]Department of Urology, Shanghai Changhai Hospital, Naval Medical University, ( https://ror.org/02bjs0p66) Shanghai, 200433 China

Article

Publisher ID: 493

DOI: 10.1186/s11658-023-00493-2

PMC ID: 10612268

PubMed ID: 37891494

SO-VID: a661feaf-9545-47da-953d-0dae63b8e74c

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/.

History

Date received : 29 May 2023

Date accepted : 20 September 2023

Funding

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

Award ID: 81971337

Award ID: 81830085

Award ID: 81972268

Award Recipient : Jinfeng Huang Fang Wang

Funded by: FundRef http://dx.doi.org/10.13039/100017950, Shanghai Municipal Health Commission;

Award ID: 20224Y0105

Award Recipient : Yiqing Zhu

Funded by: FundRef http://dx.doi.org/10.13039/100007219, Natural Science Foundation of Shanghai;

Award ID: 22ZR1477000

Award ID: 23ZR1477300

Award Recipient : Bang Xiao

Custom metadata

Keywords: oncofetal lncrna,hepatocellular carcinoma,stemness maintenance,rrna 2′-o-methylation,n6-methyladenosine

Data availability:

Keywords: oncofetal lncrna, hepatocellular carcinoma, stemness maintenance, rrna 2′-o-methylation, n6-methyladenosine

N6-methyladenosine-modified oncofetal lncRNA MIR4435-2HG contributed to stemness features of hepatocellular carcinoma cells by regulating rRNA 2′-O methylation

Read this article at

Abstract

Background

Methods

Results

Conclusions

Supplementary Information

Related collections

Karger: Oncology

Most cited references 37

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses

Functional Classification and Experimental Dissection of Long Noncoding RNAs

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 430

Cited by 4

Most referenced authors 680