Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Gastric Cancer | Research article

Ago HITS-CLIP expands microRNA-mRNA interactions in nucleus and cytoplasm of gastric cancer cells

Authors: Xinyi Zhang, Bo Shen, Yalei Cui

Published in: BMC Cancer | Issue 1/2019

Login to get access

Abstract

Background

Intensive investigations have identified a collection of microRNAs (miRNAs) and their functional machineries in cytoplasm. However, a comprehensive view of miRNAs and mRNAs in cytoplasm and nucleus has not been explored. This study aims to reveal the mechanisms of miRNA-RNA interactions in nucleus and cytoplasm.

Methods

In this study, the miRNAs and their target mRNAs in the Argonaute2 (Ago2) complex of nucleus and cytoplasm of gastric cancer cells were characterized using high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP). Then, the selected miRNAs were verified by Northern blot. The target mRNAs in the Argonaute2 (Ago2) complex of nucleus and cytoplasm of gastric cancer cells were analyzed through Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis.

Results

The results revealed that there were 243 miRNAs and 265 miRNAs in the Ago2 complexes of nucleus and cytoplasm, respectively. The majority of mature miRNAs existed in cytoplasm. The analysis of miRNA targetome from the Ago2 complexes indicated that a lot of mRNAs with high expression level existed in nucleus. The target genes of miRNAs in the Ago2 complexes of nucleus and cytoplasm played important roles in cell proliferation, cell differentiation, innate immune response and tumorigenesis.

Conclusions

microRNA-mRNA interactions occur in nucleus and cytoplasm of gastric cancer cells.
Therefore, our study demonstrated that miRNA-mRNA interactions not only took place in cytoplasm but also in nucleus.
Literature
1.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.CrossRef
2.
Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11(9):597–610.CrossRef
3.
Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425(6956):415–9.CrossRef
4.
Shu L, Zhang X. Shrimp miR-12 suppresses white spot syndrome virus infection by synchronously triggering antiviral phagocytosis and apoptosis pathways. Front Immunol. 2017;8:855.CrossRef
5.
He Y, Ma T, Zhang X. The mechanism of synchronous precise regulation of two shrimp white spot syndrome virus targets by a viral microRNA. Front Immunol. 2017;8:1546.CrossRef
6.
Ren Q, Huang X, Cui Y, Sun J, Wang W, Zhang X. Two white spot syndrome virus microRNAs target the dorsal gene to promote virus infection in Marsupenaeus japonicas shrimp. J Virol. 2017;91:e02261–16.CrossRef
7.
Yang G, Yang L, Zhao Z, Wang J, Zhang X. Signature miRNAs involved in the innate immunity of invertebrates. PLoS One. 2012;7(6):e39015.CrossRef
8.
Roberts TC. The MicroRNA biology of the mammalian nucleus. Mol Ther Nucleic Acids. 2014;3:e188.CrossRef
9.
Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, et al. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell. 2004;15:185–97.CrossRef
10.
Khudayberdiev SA, Zampa F, Rajman M, Schratt G. A comprehensive characterization of the nuclear microRNA repertoire of post-mitotic neurons. Front Mol Neurosci. 2013;6:43.CrossRef
11.
Gagnon KT, Li L, Chu Y, Janowski BA, Corey DR. RNAi factors are present and active in human cell nuclei. Cell Rep. 2014;6:211–21.CrossRef
12.
Castel SE, Martienssen RA. RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat Rev Genet. 2013;14:100–12.
13.
Rudel S, Flatley A, Weinmann L, Kremmer E, Meister G. A multifunctional human Argonaute2-specific monoclonal antibody. RNA. 2008;14:1244–53.CrossRef
14.
Chu Y, Yue X, Younger ST, Janowski BA, Corey DR. Involvement of argonaute proteins in gene silencing and activation by RNAs complementary to a non-coding transcript at the progesterone receptor promoter. Nucleic Acids Res. 2010;38:7736–48.CrossRef
15.
Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, et al. Combinatorial microRNA target predictions. Nat Genet. 2005;37:495–500.CrossRef
16.
Rajewsky N. microRNA target predictions in animals. Nat Genet. 2006;38(Suppl):S8–13.CrossRef
17.
Bentwich I. Prediction and validation of microRNAs and their targets. FEBS Lett. 2005;579:5904–10.CrossRef
18.
Cui Y, Huang T, Zhang X. RNA editing of microRNA prevents RNA-induced silencing complex recognition of target mRNA. Open Biol. 2015;5:150126.CrossRef
19.
Chi SW, Zang JB, Mele A, Darnell RB. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature. 2009;460:479–86.CrossRef
20.
Gene Ontology Consortium. The gene ontology (GO) project in 2006. Nucleic Acids Res. 2006;34:D322–6.CrossRef
21.
Leucci E, Patella F, Waage J, Holmstrom K, Lindow M, et al. microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus. Sci Rep. 2013;3:2535.CrossRef
22.
Rossi JJ. A novel nuclear miRNA mediated modulation of a non-coding antisense RNA and its cognate sense coding mRNA. EMBO J. 2011;30:4340–1.CrossRef
23.
Foldes-Papp Z, Konig K, Studier H, Buckle R, Breunig HG, et al. Trafficking of mature miRNA-122 into the nucleus of live liver cells. Curr Pharm Biotechnol. 2009;10:569–78.CrossRef
24.
Castanotto D, Lingeman R, Riggs AD, Rossi JJ. CRM1 mediates nuclear-cytoplasmic shuttling of mature microRNAs. Proc Natl Acad Sci U S A. 2009;106:21655–9.CrossRef
25.
Weinmann L, Hock J, Ivacevic T, Ohrt T, Mutze J, et al. Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell. 2009;136:496–507.CrossRef
26.
27.
Bosher JM, Dufourcq P, Sookhareea S, Labouesse M. RNA interference can target pre-mRNA: consequences for gene expression in a Caenorhabditis elegans operon. Genetics. 1999;153:1245–56.PubMedPubMedCentral
28.
Robb GB, Brown KM, Khurana J, Rana TM. Specific and potent RNAi in the nucleus of human cells. Nat Struct Mol Biol. 2005;12:133.CrossRef
29.
Kim DH, Saetrom P, Snove O Jr, Rossi JJ. MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci U S A. 2008;105:16230–5.CrossRef
30.
Ameyar-Zazoua M, Rachez C, Souidi M, Robin P, Fritsch L, Young R, et al. Argonaute proteins couple chromatin silencing to alternative splicing. Nat Struct Mol Biol. 2012;19:998–1004.CrossRef
Metadata
Title
Ago HITS-CLIP expands microRNA-mRNA interactions in nucleus and cytoplasm of gastric cancer cells
Authors
Xinyi Zhang
Bo Shen
Yalei Cui
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5246-0

Other articles of this Issue 1/2019

BMC Cancer 1/2019 Go to the issue

Research article

Recursive partitioning analysis of patients with oligometastatic non-small cell lung cancer: a retrospective study

Research article

The effects of photodynamic therapy on leukemia cells mediated by KillerRed, a genetically encoded fluorescent protein photosensitizer

Research article

Role of delayed salvage bevacizumab at symptomatic progression of chemorefractory glioblastoma

Research article

Shikonin inhibits cancer cell cycling by targeting Cdc25s

Research article

Genetic polymorphisms of vascular endothelial growth factor (VEGF) associated with gastric cancer recurrence after curative resection with adjuvant chemotherapy

Research article

Identifying the need for specialized palliative care in adult cancer patients – development and validation of a screening procedure based on proxy assessment by physicians and filter questions
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits