SCIRT lncRNA Restrains Tumorigenesis by Opposing Transcriptional Programs of Tumor-Initiating Cells

Zagorac, Sladjana; Giorgio, Alex de; Dabrowska, Aleksandra; Kalisz, Mark; Casas-Vila, Núria; Cathcart, Paul; Yiu, Angela; Ottaviani, Silvia; Degani, Neta; Lombardo, Ylenia; Alistair, Tweedie; Nissan, Tracy; Vance, Keith W.; Ulitsky, Igor; Stebbing, Justin; Castellano, Leandro

doi:10.1158/0008-5472.can-20-2612

Cited by 18 publications

(20 citation statements)

References 49 publications

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“…Although SCIRT is overexpressed in breast cancer, it interacts with EZH2 to increase the affinity of EZH2 binding to FOXM1, while SCIRT does not directly interact with FOXM1. With this capacity, SCIRT induces the expression of genes involved in the cell cycle to antagonize EZH2‐mediated effects on target genes to suppress breast cancer development 14 . Our study observed SCIRT downregulation in OSCC.…”

Section: Discussionmentioning

confidence: 60%

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LncRNA SCIRT absorbs miR‐221 to advance the expression of lncRNA GAS5 in oral squamous cell carcinoma to inhibit cancer cell apoptosis

Yang

Wang

et al. 2021

J Oral Pathology Medicine

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Background Although SCIRT has been reported to suppress breast cancer, its role in other cancers, such as oral squamous cell carcinoma (OSCC), is hardly known. We predicted that SCIRT might interact with miR‐221 to target lncRNA GAS5 and analyzed the interaction between SCIRT and miR‐221 in OSCC. Methods SCIRT and miR‐221 expression levels were quantified using RT‐qPCR. SCIRT subcellular localization was analyzed by subcellular fractionation assay. RNA pull‐down assay was applied to study the interaction between SCIRT and miR‐221. The role of SCIRT and miR‐221 in regulating GAS5 expression was analyzed by overexpression assay and RT‐qPCR. Cell apoptosis was analyzed by flow cytometry. Results SCIRT and GAS5 were downregulated, while miR‐221 was overexpressed in OSCC. SCIRT was detected in both nucleus and cytoplasm and directly interacted with miR‐221, while SCIRT overexpression failed to affect miR‐221 expression. In addition, GAS5 expression was increased by SCIRT and decreased by miR‐221. Moreover, SCIRT suppressed the role of miR‐221 in suppressing GAS5 expression and OSCC cell apoptosis. Conclusion SCIRT sponges miR‐221 to upregulate lncRNA GAS5 in OSCC and inhibit cancer cell apoptosis.

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Section: Discussionmentioning

confidence: 60%

“…LncRNAs, which lack protein‐coding information, regulate gene expression to affect cancers, suggesting their potential roles as targets for targeted cancer therapy. SCIRT is a lncRNA that suppresses breast cancer 13,14 . The role of SCIRT in other cancers, such as OSCC, is hardly known.…”

Section: Introductionmentioning

confidence: 99%

LncRNA SCIRT absorbs miR‐221 to advance the expression of lncRNA GAS5 in oral squamous cell carcinoma to inhibit cancer cell apoptosis

Yang

Wang

et al. 2021

J Oral Pathology Medicine

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“…Gene microarray was applied to compare HR-treated with untreated control HUVECs. Among the top 20 significantly upregulated lncRNAs in the HR-treated vs. control group, SCIRT, a reported tumor repressor [ 33 ], exhibited the highest angiogenesis correlation score ( Figure 2(a) ). The increase of SCIRT induced by HR treatment was further confirmed by qRT-PCR ( Figure 2(b) ).…”

Section: Resultsmentioning

confidence: 99%

Long Noncoding RNA SCIRT Promotes HUVEC Angiogenesis via Stabilizing VEGFA mRNA Induced by Hypoxia

Gao

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Ischemia-reperfusion injury (IRI) is closely associated the abnormal expression of long noncoding RNAs (lncRNAs), especially for their regulatory roles in IRI-related angiogenesis. This study applied a hypoxia-reoxygenation (HR) cell model to simulate the IRI condition, as well as RNA sequencing and RNA pull-down experiments to reveal roles of the lncRNA and Stem Cell Inhibitory RNA Transcript (SCIRT), in endothelial angiogenesis. We found that SCIRT was increased under the HR condition and exhibited a high expression correlation with angiogenesis marker VEGFA. RNA-seq data analysis further revealed that VEGFA-related angiogenesis was regulated by SCIRT in HUVECs. Gain and loss of function experiments proved that SCIRT posttranscriptionally regulated VEGFA via affecting its mRNA stability. Furthermore, HuR (ELAVL1), an RNA binding protein (RBP), was identified as a SCIRT-binding partner, which bound and stabilized VEGFA. Moreover, SCIRT promoted HuR expression posttranslationally by inhibiting its ubiquitination under the HR condition. These findings reveal that lncRNA SCIRT can mediate endothelial angiogenesis by stabilizing the VEGFA mRNA via modulating RBP HuR stability under the HR condition.

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“…A newly identified lncRNA, stem cell inhibitory RNA transcript (SCIRT), acts as the facilitator for exosomal loading of miR-665. SCIRT was reported to play a crucial role in cancer cell state transitions by direct interaction with chromatin modifier EZH2, then inhibiting cancer cells' self-renewal process [ 25 ]. Our findings that SCIRT might promote the selective sorting of critical exo-miRNAs into cancer cell exosomes further extend our understanding of its role in tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Exosomal lncRNA SCIRT/miR-665 Transferring Promotes Lung Cancer Cell Metastasis through the Inhibition of HEYL

Wang

Lin

et al. 2021

Journal of Oncology

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Lung cancer remains the leading cause of cancer-related death worldwide. Recently, extracellular vesicles such as exosomes have attracted considerable interest both as a source for theranostic biomarkers and an essential participant in lung cancer progression. However, how specific exosomal cargos, such as noncoding RNAs, are selectively packaged into exosomes and promote lung cancer progression remains unclear. In this study, we identified miR-665 as the most elevated exosomal miRNA from both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) patients. We further demonstrated that lncRNA SCIRT was also increased in cancer cell exosomes and may facilitate the exosomal loading of miR-665 with the help of hnRNPA1. As a consequence, exosomal miR-665 promoted lung cancer cell invasion and migration by targeting Notch downstream transcription factor HEYL. In addition, we found that miR-665 and SCIRT were significantly upregulated in tumor tissue and plasma of patients with lung cancer, and both of them showed increased expression in metastatic disease samples. Our findings suggest that the exosomal transferring of miR-665 and SCIRT is a functional and mechanism-driven pathway that contributes to cancer progression and, thus, may provide novel diagnostic and therapeutic targets for lung cancer.

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SCIRT lncRNA Restrains Tumorigenesis by Opposing Transcriptional Programs of Tumor-Initiating Cells

Abstract: et al. (2020) SCIRT lncRNA restrains tumorigenesis by opposing transcriptional programs of tumor-initiating cells. Cancer Research.

Cited by 18 publications

References 49 publications

LncRNA SCIRT absorbs miR‐221 to advance the expression of lncRNA GAS5 in oral squamous cell carcinoma to inhibit cancer cell apoptosis

LncRNA SCIRT absorbs miR‐221 to advance the expression of lncRNA GAS5 in oral squamous cell carcinoma to inhibit cancer cell apoptosis

Long Noncoding RNA SCIRT Promotes HUVEC Angiogenesis via Stabilizing VEGFA mRNA Induced by Hypoxia

Exosomal lncRNA SCIRT/miR-665 Transferring Promotes Lung Cancer Cell Metastasis through the Inhibition of HEYL

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