A Kelch domain-containing KLHDC7B and a long non-coding RNA ST8SIA6-AS1 act oppositely on breast cancer cell proliferation via the interferon signaling pathway

Jeong, Gookjoo; Bae, Hansol; Jeong, Dawoon; Ham, Juyeon; Park, Sung-Bin; Kim, Hyeon Woo; Kang, Hyejin; Kim, Sun Jung

doi:10.1038/s41598-018-31306-8

Cited by 46 publications

(37 citation statements)

References 34 publications

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“…Previous studies suggest that the overexpression of protein members of the Kelch family, such as KLHL2, increases apoptosis (Tseng and Bixby, ) or, in the case of silencing KLHDC7B, favors death resistance, as previously published (Jeong et al ., ). Here, we show that the silencing of LncKLHDC7B led to resistance to cell death.…”

Section: Discussionmentioning

confidence: 97%

Expression of long non‐coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple‐negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death

et al. 2019

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Triple negative breast cancer ( TNBC ) represents an aggressive phenotype with poor prognosis compared with ER , PR, and HER 2‐positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non‐coding RNA (lnc RNA ) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lnc RNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of Lnc KLHDC 7B ( ENSG 00000226738 ). A total of 710 lnc RNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lnc RNA were independently validated. We discovered that Lnc KLHDC 7B ( ENSG 00000226738 ) acts as a transcriptional modulator of its neighboring coding gene KLHDC 7B in the immunomodulatory subtype. Furthermore, Lnc KLHDC 7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of Lnc KLHDC 7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of Lnc KLHDC 7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC 7B and Lnc KLHDC 7B is associated with poor prognosis in patients with breast cancer.

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Section: Discussionmentioning

confidence: 97%

Expression of long non‐coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple‐negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death

et al. 2019

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“…More specifically, the solute carrier family 7 (anionic amino acid transporter light chain), member 11 (SLC7A11) and interleukin 20 receptor-β (IL20RB) were upregulated in the in the presence of siRNAs. Kelch domain containing 7B (KLHDC7B), which has been associated with gene modulation activity in the interferon signalling pathway [ 39 ], was also upregulated after the snoRNA knock-down (fold-change of 83.3). Drosophila Roundabout homolog 4 (ROBO4), an axon guidance receptor, which increases cell adhesion [ 40 ], correlating with an epithelial phenotype, was also upregulated (fold-change of 73.09).…”

Section: Resultsmentioning

confidence: 99%

jouvence, a new human snoRNA involved in the control of cell proliferation

2020

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Background Small nucleolar RNAs (snoRNAs) are non-coding RNAs that are conserved from archaebacteria to mammals. They are associated in the nucleolus, with proteins to form small nucleolar ribonucleoprotein (snoRNPs). They modify ribosomal RNAs, for example, the H/ACA box that converts uridine to pseudouridine. In humans, various pathologies have been associated with snoRNAs, and several snoRNAs have been reported to participate in many cancer processes. Recently, a new H/ACA box snoRNA named jouvence has been identified in Drosophila and has been shown to be involved in lifespan determination in relation to gut homeostasis. Because snoRNAs are conserved through evolution, both structurally and functionally, a jouvence orthologue has been identified in humans. RT-PCR has revealed that jouvence is expressed, suggesting that it might be functional. These results suggest the hypothesis that jouvence may display similar functions, including increasing the healthy lifespan in humans. Results Here, we report the characterization of the human snoRNA jouvence, which has not yet been annotated in the genome. We show that its overexpression significantly stimulates cell proliferation, both in various stable cancerous cell lines as well as in primary cells. By contrast, its knockdown by siRNA leads to the opposite phenotype, a rapid decrease in cell proliferation. Transcriptomic analysis (RNA-Seq) revealed that the overexpression of jouvence leads to a dedifferentiation signature of the cells. Conversely, the knockdown of jouvence led to a striking decrease in the expression levels of genes involved in ribosome biogenesis and the spliceosome. Conclusion The overexpression of a single and short non-coding RNA of 159 nucleotides, the snoRNA-jouvence, seems to be sufficient to reorient cells toward stemness, while its depletion blocks cell proliferation. In this context, we speculate that the overexpression of jouvence, which appears to be a non-canonical H/ACA snoRNA, could represent a new tool to fight against the deleterious effects of aging, while inversely, its knockdown by siRNA could represent a new approach in cancer therapy.

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“…More specifically, the Solute Carrier family 7 (anionic amino acid transporter light chain, xc-system), member 11 (SLC7A11) and interleukin 20 receptor- (IL20RB) are upregulated in the siRNA condition. Kelch domain containing 7B (KLHDC7B), which has been associated with gene modulation activity in the Interferon signaling pathway [38], is also upregulated after h-jou knock-down (fold-change of 83,3). Roundabout, axon guidance receptor, homolog 4 Drosophila (ROBO4) which increases cell adhesion [39] and correlates with an epithelial phenotype, is upregulated (with a fold-change of 73,09).…”

Section: Knockdown Of H-jou By Sirna Decreases the Ribosome Biogenesimentioning

confidence: 99%

jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

El-Khoury

Bignon

Martin

2020

Preprint

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Small nucleolar RNAs (snoRNAs) are non-coding RNAs conserved from archeobacteria to mammals. In humans, various snoRNAs have been associated with pathologies as well as with cancer. Recently in Drosophila, a new snoRNA named jouvence has been involved in lifespan.Since snoRNAs are well conserved through evolution, both structurally and functionally, jouvence orthologue has been identified in human, allowing hypothesizing that jouvence could display a similar function (increasing healthy lifespan) in human. Here, we report the characterization of the human snoRNA-jouvence, which was not yet annotated in the genome.We show, both in stably cancerous cell lines and in primary cells, that its overexpression stimulates the cell proliferation. In contrast, its knockdown, by siRNA leads to an opposite phenotype, a decrease in cell proliferation. Transcriptomic analysis reveals that overexpression of jouvence leads to a dedifferentiation signature of the cells, a cellular effect comparable to rejuvenation. Inversely, the knockdown of jouvence leads to a decrease of genes involved in ribosomes biogenesis and spliceosome in agreement with the canonical role of a H/ACA box snoRNA. In this context, jouvence could represent a now tool to fight against the deleterious effect of aging, as well as a new target in cancer therapy.

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A Kelch domain-containing KLHDC7B and a long non-coding RNA ST8SIA6-AS1 act oppositely on breast cancer cell proliferation via the interferon signaling pathway

Cited by 46 publications

References 34 publications

Expression of long non‐coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple‐negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death

Expression of long non‐coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple‐negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death

jouvence, a new human snoRNA involved in the control of cell proliferation

jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

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