The hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells.

Hdl Handle:
http://hdl.handle.net/10034/604377
Title:
The hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells.
Authors:
Pickard, Mark R.; Williams, Gwyn T.
Abstract:
Growth arrest-specific 5 (GAS5) lncRNA promotes apoptosis, and its expression is down-regulated in breast cancer. GAS5 lncRNA is a decoy of glucocorticoid/related receptors; a stem-loop sequence constitutes the GAS5 hormone response element mimic (HREM), which is essential for the regulation of breast cancer cell apoptosis. This preclinical study aimed to determine if the GAS5 HREM sequence alone promotes the apoptosis of breast cancer cells. Nucleofection of hormone-sensitive and -insensitive breast cancer cell lines with a GAS5 HREM DNA oligonucleotide increased both basal and ultraviolet-C-induced apoptosis, and decreased culture viability and clonogenic growth, similar to GAS5 lncRNA. The HREM oligonucleotide demonstrated similar sequence specificity to the native HREM for its functional activity and had no effect on endogenous GAS5 lncRNA levels. Certain chemically modified HREM oligonucleotides, notably DNA and RNA phosphorothioates, retained pro-apoptotic. activity. Crucially the HREM oligonucleotide could overcome apoptosis resistance secondary to deficient endogenous GAS5 lncRNA levels. Thus, the GAS5 lncRNA HREM sequence alone is sufficient to induce apoptosis in breast cancer cells, including triple-negative breast cancer cells. These findings further suggest that emerging knowledge of structure/function relationships in the field of lncRNA biology can be exploited for the development of entirely novel, oligonucleotide mimic-based, cancer therapies.
Affiliation:
Keele University
Citation:
Pickard, M. R., & Williams, G. T. (2016). The hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells. Oncotarget, 7(9), 10104-10116. DOI: 10.18632/oncotarget.7173
Publisher:
Impact Journals
Journal:
Oncotarget
Publication Date:
3-Feb-2016
URI:
http://hdl.handle.net/10034/604377
DOI:
10.18632/oncotarget.7173
PubMed ID:
26862727
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/26862727
Type:
Article
Language:
en
EISSN:
1949-2553
Sponsors:
Breast Cancer Now
Appears in Collections:
Institute of Medicine

Full metadata record

DC FieldValue Language
dc.contributor.authorPickard, Mark R.en
dc.contributor.authorWilliams, Gwyn T.en
dc.date.accessioned2016-04-04T13:23:40Zen
dc.date.available2016-04-04T13:23:40Zen
dc.date.issued2016-02-03en
dc.identifier.citationPickard, M. R., & Williams, G. T. (2016). The hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells. Oncotarget, 7(9), 10104-10116. DOI: 10.18632/oncotarget.7173en
dc.identifier.pmid26862727en
dc.identifier.doi10.18632/oncotarget.7173en
dc.identifier.urihttp://hdl.handle.net/10034/604377en
dc.description.abstractGrowth arrest-specific 5 (GAS5) lncRNA promotes apoptosis, and its expression is down-regulated in breast cancer. GAS5 lncRNA is a decoy of glucocorticoid/related receptors; a stem-loop sequence constitutes the GAS5 hormone response element mimic (HREM), which is essential for the regulation of breast cancer cell apoptosis. This preclinical study aimed to determine if the GAS5 HREM sequence alone promotes the apoptosis of breast cancer cells. Nucleofection of hormone-sensitive and -insensitive breast cancer cell lines with a GAS5 HREM DNA oligonucleotide increased both basal and ultraviolet-C-induced apoptosis, and decreased culture viability and clonogenic growth, similar to GAS5 lncRNA. The HREM oligonucleotide demonstrated similar sequence specificity to the native HREM for its functional activity and had no effect on endogenous GAS5 lncRNA levels. Certain chemically modified HREM oligonucleotides, notably DNA and RNA phosphorothioates, retained pro-apoptotic. activity. Crucially the HREM oligonucleotide could overcome apoptosis resistance secondary to deficient endogenous GAS5 lncRNA levels. Thus, the GAS5 lncRNA HREM sequence alone is sufficient to induce apoptosis in breast cancer cells, including triple-negative breast cancer cells. These findings further suggest that emerging knowledge of structure/function relationships in the field of lncRNA biology can be exploited for the development of entirely novel, oligonucleotide mimic-based, cancer therapies.en
dc.description.sponsorshipBreast Cancer Nowen
dc.language.isoenen
dc.publisherImpact Journalsen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/26862727en
dc.subjectapoptosisen
dc.subjectbreast canceren
dc.subjectlncRNAen
dc.subjectoligonucleotide therapyen
dc.subjectGAS5en
dc.titleThe hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells.en
dc.typeArticleen
dc.identifier.eissn1949-2553en
dc.contributor.departmentKeele Universityen
dc.identifier.journalOncotargeten

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