Endocrine therapy-resistant breast cancer model cells are inhibited by soybean glyceollin I through Eleanor non-coding RNA

Yamamoto, Takaya; Sakamoto, Chiyomi; Tachiwana, Hiroaki; Kumabe, Mitsuru; Matsui, Toshiro; Yamashita, Tadatoshi; Shinagawa, Masatoshi; Ochiai, Koji; Saitoh, Noriko; Nakao, Mitsuyoshi

doi:10.1038/s41598-018-33227-y

Cited by 23 publications

(28 citation statements)

References 43 publications

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“…3c and Supplementary Fig. 5c), in good agreement with the fact that LTED cells undergo apoptosis upon resveratrol treatment 34 . The expression levels of other genes in 6q21, SNX , and LACE1 were reduced (Fig.…”

Section: Resultssupporting

confidence: 84%

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The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

et al. 2019

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MCF7 cells acquire estrogen-independent proliferation after long-term estrogen deprivation (LTED), which recapitulates endocrine therapy resistance. LTED cells can become primed for apoptosis, but the underlying mechanism is largely unknown. We previously reported that Eleanor non-coding RNAs (ncRNAs) upregulate the ESR1 gene in LTED cells. Here, we show that Eleanors delineate the topologically associating domain (TAD) of the ESR1 locus in the active nuclear compartment of LTED cells. The TAD interacts with another transcriptionally active TAD, which is 42.9 Mb away from ESR1 and contains a gene encoding the apoptotic transcription factor FOXO3. Inhibition of a promoter-associated Eleanor suppresses all genes inside the Eleanor TAD and the long-range interaction between the two TADs, but keeps FOXO3 active to facilitate apoptosis in LTED cells. These data indicate a role of ncRNAs in chromatin domain regulation, which may underlie the apoptosis-prone nature of therapy-resistant breast cancer cells and could be good therapeutic targets.

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Section: Resultssupporting

confidence: 84%

“…Resveratrol induces apoptosis in LTED cells 34 . The present study showed that pa-Eleanor(S) is a target of resveratrol (Fig.…”

Section: Discussionmentioning

confidence: 99%

The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

et al. 2019

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“…Suppression of Eleanor RNAs reduces the ESR1 transcription. Therefore, Eleanors may be a good therapeutic target for breast cancers 25,43,44 . However, the mechanism by which Eleanor RNAs stimulate the ESR1 transcription has remained enigmatic.…”

Section: Discussionmentioning

confidence: 99%

Nucleosome destabilization by nuclear non-coding RNAs

et al. 2020

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In the nucleus, genomic DNA is wrapped around histone octamers to form nucleosomes. In principle, nucleosomes are substantial barriers to transcriptional activities. Nuclear noncoding RNAs (ncRNAs) are proposed to function in chromatin conformation modulation and transcriptional regulation. However, it remains unclear how ncRNAs affect the nucleosome structure. Eleanors are clusters of ncRNAs that accumulate around the estrogen receptor-α (ESR1) gene locus in long-term estrogen deprivation (LTED) breast cancer cells, and markedly enhance the transcription of the ESR1 gene. Here we detected nucleosome depletion around the transcription site of Eleanor2, the most highly expressed Eleanor in the LTED cells. We found that the purified Eleanor2 RNA fragment drastically destabilized the nucleosome in vitro. This activity was also exerted by other ncRNAs, but not by poly(U) RNA or DNA. The RNA-mediated nucleosome destabilization may be a common feature among natural nuclear RNAs, and may function in transcription regulation in chromatin.

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“…Thus, the functions of u-Eleanor and pa-Eleanor suggest that the regulation of Eleanor expression may represent a new treatment strategy for breast cancer adapted to estrogen-deprived conditions. Consistent with this idea, resveratrol and glyceollin I, phytoalexins that are synthesized in plants under stress conditions, decrease the expression of Eleanors to induce apoptotic death in LTED cells [122].…”

Section: Lncrnas Belonging To Multiple Categoriesmentioning

confidence: 61%

Long Noncoding RNAs Involved in the Endocrine Therapy Resistance of Breast Cancer

Takeiwa

Ikeda

Mitobe

et al. 2020

Cancers

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Long noncoding RNAs (lncRNAs) are defined as RNAs longer than 200 nucleotides that do not encode proteins. Recent studies have demonstrated that numerous lncRNAs are expressed in humans and play key roles in the development of various types of cancers. Intriguingly, some lncRNAs have been demonstrated to be involved in endocrine therapy resistance for breast cancer through their own mechanisms, suggesting that lncRNAs could be promising new biomarkers and therapeutic targets of breast cancer. Here, we summarize the functions and mechanisms of lncRNAs related to the endocrine therapy resistance of breast cancer.

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Endocrine therapy-resistant breast cancer model cells are inhibited by soybean glyceollin I through Eleanor non-coding RNA

Cited by 23 publications

References 43 publications

The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

Nucleosome destabilization by nuclear non-coding RNAs

Long Noncoding RNAs Involved in the Endocrine Therapy Resistance of Breast Cancer

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