Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition

Wang, Jing; Chen, Dengyu; He, Xue; Zhang, Yuxia; Shi, Fangfang; Wu, Di; Chen, Jun Song; Zhang, Ying; Zhao, Fengsu; Dou, Jun

doi:10.1186/s12935-015-0174-4

Cited by 35 publications

(33 citation statements)

References 34 publications

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“…NRAD1, therefore, joins a shortlist of lncRNAs that have been described as functionally associated with CSCs. For example, lncRNAs HOTAIR, MALAT-1, linc-ROR, lncRNA-Hh, lincRNA-21, LINC00617, and HULC in the putative CSCs of cell lines increased self-renewal and tumorigenicity [52][53][54][55][56][57][58][59]. The lncRNA TUG1 is upregulated in glioblastoma CSCs and promotes their self-renewal by sponging miR-145 and recruiting polycomb repressive complex 2 (PRC2) to repress genes required for differentiation [60].…”

Section: Discussionmentioning

confidence: 99%

ALDH1A3-regulated long non-coding RNA NRAD1 is a potential novel target for triple-negative breast tumors and cancer stem cells

et al. 2019

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To discover novel therapeutic targets for triple-negative breast cancer (TNBC) and cancer stem cells (CSCs), we screened long non-coding RNAs (lncRNAs) most enriched in TNBCs for high expression in CSCs defined by high Aldefluor activity and associated with worse patient outcomes. This led to the identification of non-coding RNA in the aldehyde dehydrogenase 1 A pathway (NRAD1), also known as LINC00284. Targeting NRAD1 in TNBC tumors using antisense oligonucleotides reduced cell survival, tumor growth, and the number of cells with CSC characteristics. Expression of NRAD1 is regulated by an enzyme that causes Aldefluor activity in CSCs, aldehyde dehydrogenase 1A3 (ALDH1A3) and its product retinoic acid. Cellular fractionation revealed that NRAD1 is primarily nuclear localized, which suggested a potential function in gene regulation. This was confirmed by transcriptome profiling and chromatin isolation by RNA purification, followed by sequencing (ChIRP-seq), which demonstrated that NRAD1 has enriched chromatin interactions among the genes it regulates. Gene Ontology enrichment analysis revealed that NRAD1 regulates expression of genes involved in differentiation and catabolic processes. NRAD1 also contributes to gene expression changes induced by ALDH1A3; thereby, the induction of NRAD1 is a novel mechanism through which ALDH1A3 regulates gene expression. Together, these data identify lncRNA NRAD1 as a downstream effector of ALDH1A3, and a target for TNBCs and CSCs, with functions in cell survival and regulation of gene expression.

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Section: Discussionmentioning

confidence: 99%

ALDH1A3-regulated long non-coding RNA NRAD1 is a potential novel target for triple-negative breast tumors and cancer stem cells

et al. 2019

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“…19,20 In the ovarian cancer, inhibited HOTAIR expression in ovarian cancer cells could impede the tumourgenesis and metastasis. 21,22 According to Deng et al, HOTAIR modulates the self-renewal, growth, tumour metastatic and formation of the cancer stem-like cell subpopulation enriched from breast cancer cells. 23 Moreover, the levels of IGF1 are elevated and may affect ovarian function and increase androgen production in PCOS.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulated lncRNA HOTAIR alleviates polycystic ovaries syndrome in rats by reducing expression of insulin‐like growth factor 1 via microRNA‐130a

Jiang

Xue

et al. 2019

J Cellular Molecular Medi

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It has been found that long noncoding RNA HOTAIR, microRNA‐130a (miR‐130a) and insulin‐like growth factor 1 (IGF1) expression are associated with ovarian cancer, thus, we hypothesised that the HOTAIR/miR‐130a/IGF1 axis might associate with endocrine disorders and biological behaviours of ovarian granulosa cells in rat models of polycystic ovary syndrome (PCOS). PCOS rat models were established by injection of dehydro‐isoandrosterone, followed by treatment of si‐HOTAIR, oe‐HOTAIR, miR‐130a mimics or miR‐130a inhibitors. Serum hormonal levels were determined to evaluate endocrine conditions. The effect of HOTAIR and miR‐130a on activities of isolated ovarian granulosa cells was assessed, as well as the involvement of IGF1.In the ovarian tissues and granulosa cells of PCOS rat models, highly expressed HOTAIR and IGF1 and poorly expressed miR‐130a were identified. In response to oe‐HOTAIR, serum levels of E2, T and LH were increased and serum levels of FSH were reduced; the proliferation of granulosa cells was reduced and apoptosis was promoted; notably, expression of miR‐130a was reduced while expression of IGF1 was increased. The treatment of si‐HOTAIR reversed the situation. Furthermore, the binding of HOTAIR to miR‐130a and targeting relationship of miR‐130a and IGF1 were confirmed. LncRNA HOTAIR up‐regulates the expression of IGF1 and aggravates the endocrine disorders and granulosa cell apoptosis through competitive binding to miR‐130a in rat models of PCOS. Based on our finding, we predict that competitive binding of HOTAIR to miR‐130a may act as a novel target for the molecular treatment of PCOS.

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“…The down-regulation of HOTAIR has resulted in a marked decrease in CSC migration and invasion and significantly diminished the tumor growth and lung metastasis in xenograft mice. Consequently, this strategy has been suggested as a promising novel modality for future clinical trials [49] . HOTAIR is overexpressed in SOC tissues compared with normal controls.…”

Section: Hox Transcript Antisense Rna (Hotair)mentioning

confidence: 99%

The Role of Long Non-Coding RNAs in Ovarian Cancer

Nikpayam

Tasharrofi

Sarrafzadeh

et al. 2017

IBJ

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Background: Ovarian cancer is the most fatal tumor of female's reproductive system, and several genetics and environmental factors are involved in its development. Various studies have already identified suitable biomarkers to facilitate the early detection, prognosis evaluation, and the assessment of treatment response. However, the aim of this review was to investigate the role of long non-coding RNAs (lncRNAs) in tumorigenesis process of ovarian cancer and their potential applications as ovarian cancer biomarkers. Methods: We performed an online literature search of the MEDLINE/PubMed databases using the key words ovarian cancer, lncRNA, and biomarker. Results: We found that several lncRNAs have been shown to be deregulated in ovarian cancer and the specific mechanism of their enrollment in ovarian cancer has been defined for a few of them. In addition, expression profiling has revealed an association between lncRNAs and patients' survival, metastasis potential as well as treatment response. Conclusions: Expression profiling as well as methylation analysis of lncRNAs in ovarian cancer may lead to the identification of novel biomarkers that can help in the classification of patients based on prognosis and treatment response.

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Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition

Cited by 35 publications

References 34 publications

ALDH1A3-regulated long non-coding RNA NRAD1 is a potential novel target for triple-negative breast tumors and cancer stem cells

ALDH1A3-regulated long non-coding RNA NRAD1 is a potential novel target for triple-negative breast tumors and cancer stem cells

Down‐regulated lncRNA HOTAIR alleviates polycystic ovaries syndrome in rats by reducing expression of insulin‐like growth factor 1 via microRNA‐130a

The Role of Long Non-Coding RNAs in Ovarian Cancer

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