The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

Chakravarty, Dimple; Sboner, Andrea; Nair, Sujit S.; Γιαννοπούλου, Ευγενία; Li, Ruohan; Hennig, Sven; Mosquera, Juan Miguel; Pauwels, Jonathan; Park, Kyung; Kossaï, Myriam; MacDonald, Theresa Y.; Fontugne, Jacqueline; Erho, Nicholas; Vergara, Ismael A.; Ghadessi, Mercedeh; Davicioni, Elai; Jenkins, Robert B.; Palanisamy, Nallasivam; Chen, Zhengming; Nakagawa, Shinichi; Hirose, Tetsuro; Bander, Neil H.; Beltran, Himisha; Fox, Archa H.; Elemento, Olivier; Rubin, Mark A.

doi:10.1038/ncomms6383

Cited by 550 publications

(482 citation statements)

References 51 publications

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“…During the differentiation of embryonic stem cells and muscle cells, NEAT1 lncRNAs have been found to be upregulated (14,16). A previous study reported that estrogen receptor α-regulated NEAT1 lncRNA acted as a transcriptional regulator and promoted tumorigenesis leading to prostate adenocarcinoma in experimental animal models (34). Furthermore, NEAT1 expression was associated with oncogenic activity and metastatic progression in lung cancer (35,36).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of lncRNA NEAT1 mitigates multidrug resistance by inhibiting ABCG2 in leukemia

et al. 2016

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Abstract. Leukemia is a heterogeneous clonal disorder in which early hematopoietic cells fail to differentiate and do not undergo programmed cell death or apoptosis. Less than one-third of adult patients with leukemia are managed using current therapies due to the emergence of multidrug resistance (MDR), emphasizing the need for newer and more robust approaches. Recent reports have suggested that long non-coding RNAs (lncRNAs) contribute to selective gene expression and, hence, could be manipulated effectively to halt the progression of cancer. However, little is known regarding the role of lncRNA in leukemia. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a nuclear-restricted lncRNA involved in the pathogenesis of certain types of cancer. Deregulated expression of NEAT1 has been reported in a number of human malignancies, including leukemia and other solid tumors. The present study aimed to characterize the role of NEAT1 in the regulation of MDR in leukemia. Using reverse transcription-quantitative polymerase chain reaction, it was demonstrated that NEAT1 messenger RNA (mRNA) expression levels were significantly downregulated in leukemia patient samples compared with those from healthy donors. Furthermore, NEAT1 mRNA expression was repressed in a number of leukemia cell lines, including K562, THP-1, HL-60 and Jurkat cells, compared with peripheral white blood control cells, consistent with the expression observed in patients with leukemia. In addition, the transfection of a NEAT1 overexpression plasmid into K562 and THP-1 leukemia cell lines alleviated MDR induced by cytotoxic agents, such as Alisertib and Bortezomib, through inhibition of ATP-binding cassette G2. Although more robust studies are warranted, the current findings provide the basis for the use of NEAT1 as a novel promising target in the treatment of leukemia.

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Section: Discussionmentioning

confidence: 99%

Overexpression of lncRNA NEAT1 mitigates multidrug resistance by inhibiting ABCG2 in leukemia

et al. 2016

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“…Nuclear receptors recruit multiple enzymatically diverse epigenetic coregulators, including p160/p300 lysine acetyltransferase, demethylases that cooperate with the mediator complex to stabilize recruitment of the basal transcriptional machinery, and RNA polymerase II. (B) Evidence from genome-wide chromatin immunoprecipitation studies indicate the recruitment of AR in LNCaP, 22Rv1, VCaP PCa cells (GSM698597) (Sharma et al 2013), and ERa in VCaP (GSM1076110) (Chakravarty et al 2014) to the VEGF promoter.…”

Section: Transcriptional Regulation Of Pro-angiogenesis Pathways In Pcamentioning

confidence: 99%

Regulation of vascular endothelial growth factor in prostate cancer

Brot¹,

Ntekim²,

Cardenas³

et al. 2015

Endocrine-Related Cancer

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Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to w30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically %24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling.

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“…MALAT1 expression was higher in thyroid cancer tissues and in thyroid cancer cells than normal thyroid (Huang, et al 2016a). Likewise, NEAT1 upregulated in breast , endometrial ); ovarian ) and thyroid tumors , and is the highest lncRNA in prostate cancer and strongly associated with metastasis (Chakravarty, et al 2014). …”

Section: Examples Of Lncrnas Dysregulated In Endocrine-related Cancersmentioning

confidence: 99%

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

Klinge

2018

Endocrine-Related Cancer

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Abstract:The human genome is 'pervasively transcribed' leading to a complex array of noncoding RNAs (ncRNAs) that far outnumber coding mRNAs. ncRNAs have regulatory roles in transcription and post-transcriptional processes as well numerous cellular functions that remain to be fully described. Best characterized of the 'expanding universe' of ncRNAs are the ~ 22 nucleotide microRNAs (miRNAs) that base-pair to target mRNA's 3' untranslated region within the RNA-induced silencing complex (RISC) and block translation and may stimulate mRNA transcript degradation. Long non-coding RNAs (lncRNAs) are classified as >200 nucleotides in length, but range up to several kb and are heterogeneous in genomic origin and function.LncRNAs fold into structures that interact with DNA, RNA, and proteins to regulate chromatin dynamics, protein complex assembly, transcription, telomere biology, and splicing. Some lncRNAs act as sponges for miRNAs and decoys for proteins. Nuclear-encoded lncRNAs can be taken up by mitochondria and lncRNAs are transcribed from mtDNA. Both miRNAs and lncRNAs are dysregulated in endocrine cancers. This review provides an overview on the current understanding of the regulation and function of selected lncRNAs and miRNAs, and their interaction, in endocrine-related cancers: breast, prostate, endometrial, and thyroid.

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The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

Cited by 550 publications

References 51 publications

Overexpression of lncRNA NEAT1 mitigates multidrug resistance by inhibiting ABCG2 in leukemia

Overexpression of lncRNA NEAT1 mitigates multidrug resistance by inhibiting ABCG2 in leukemia

Regulation of vascular endothelial growth factor in prostate cancer

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

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