The hypoxia-responsive lncRNA<i>NDRG-OT1</i>promotes NDRG1 degradation via ubiquitin-mediated proteolysis in breast cancer cells

Lin, Hsin-Chen; Yeh, Ching-Ching; Chao, Lo-Yun; Tsai, Mong‐Hsun; Chen, Hung‐Hsin; Chuang, Eric Y.; Lai, Liang‐Chuan

doi:10.18632/oncotarget.23732

Cited by 34 publications

(36 citation statements)

References 37 publications

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“…Furthermore, miRNAs are capable of regulating the occurrence and development of the nervous system, and some specific miRNAs can regulate the pathophysiological processes of neurological diseases. For example, miR‐183 has been reported to share a close association with the occurrence of glioma, miRNA‐129‐2‐3p and miRNA‐935 are expressed in plasma and brain tissues of intractable epilepsy, and miR‐323a‐5p is abnormally expressed in patients with refractory epilepsy caused by focal cortical dysplasia …”

Section: Discussionmentioning

confidence: 99%

“…For example, miR-183 has been reported to share a close association with the occurrence of glioma, miRNA-129-2-3p and miRNA-935 are expressed in plasma and brain tissues of intractable epilepsy, and miR-323a-5p is abnormally expressed in patients with refractory epilepsy caused by focal cortical dysplasia. [28][29][30][31] Evidence has been provided that miR-135a-5p can inhibit tumor cell proliferation and promote the apoptosis of tumor cells in many tumors, while its role in epilepsy has yet to be adequately identified. 32 Reports have suggested that miR-135a-5p confer neuronal protection in mice with Alzheimer's disease by regulating potassium channels.…”

Section: Discussionmentioning

confidence: 99%

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Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Zheng

et al. 2019

The Kaohsiung J of Med Scie

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Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell models of epileptic seizure. The expression of lncRNA GAS5 was measured in the established rat and cell models. The binding sites between lncRNA GAS5 and miR‐135a‐5p, as well as those between miR‐135a‐5p and 3′ untranslated region of KCNQ3 were predicted by miRDB and Targetscan, separately, followed by verification using dual‐luciferase reporter gene assay. The expression of miR‐135a‐5p was measured in response to the overexpression of lncRNA GAS5. The mRNA and protein levels of KCNQ3 were examined in response to overexpression of miR‐135a‐5p. Next, the latency of epilepsy and frequency of epileptic seizures were assessed in rats injected with Lv‐shGAS5 and Lv‐miR‐135a‐5p in epileptic seizure model. In the rat and cell models, lncRNA GAS5 was highly expressed when epileptic seizure was induced. The expression of miR‐135a‐5p was decreased by overexpression of lncRNA GAS5. Meanwhile, the mRNA and protein levels of KCNQ3 were decreased in response to knockdown of miR‐135a‐5p. After the treatment of Lv‐shGAS5 and Lv‐miR‐135a‐5p, the average latent period of epilepsy was prolonged and the frequency of seizures was decreased. The key findings of the present study provide evidence emphasizing that lncRNA GAS5 functions as a competitive endogenous RNA of miR‐135a‐5p to increase expression of KCNQ3, and lncRNA GAS5 silencing inhibited the occurrence and progression of epilepsy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Zheng

et al. 2019

The Kaohsiung J of Med Scie

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“…LncRNA NDRG1-OT1 was found to be significantly upregulated in hypoxia and inhibited the expression of NDRG1 in several breast cancer cell lines [33]. Here, we further discovered that although the overall effect of NDRG1-OT1 on NDRG1 was inhibitory, different fragments of NDRG1-OT1 played various roles in regulating the target gene via recruiting different proteins.…”

Section: Discussionmentioning

confidence: 65%

“…In recent research in our laboratory, we first renamed the lncRNA lnc-NDRG1-1 as NDRG1-OT1 (NDRG1 overlapping transcript 1) according to the guidelines for non-coding RNA nomenclature [32]. NDRG1-OT1 was induced under hypoxia in breast cancer cells [33], but its function remained unclear. We discovered that ectopic expression of NDRG1-OT1 could inhibit NDRG1 expression at both RNA and protein levels [33].…”

Section: Introductionmentioning

confidence: 99%

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Different effects of long noncoding RNANDRG1-OT1fragments onNDRG1transcription in breast cancer cells under hypoxia

et al. 2018

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Hypoxia plays a crucial role in the aggressiveness of solid tumors by driving multiple signaling pathways. Recently, long non-coding RNA (lncRNA) has been reported to promote or inhibit tumor aggressiveness by regulating gene expression. Previous studies in our laboratory found that the lncRNA NDRG1-OT1 is significantly up-regulated under hypoxia and inhibits its target gene NDRG1 at both the mRNA and protein levels. At the protein level, NDRG1-OT1 increases NDRG1 degradation via ubiquitin-mediated proteolysis. However, the repressive mechanism of NDRG1 at the RNA level is still unknown. Therefore, the purpose of this study was to study how NDRG1-OT1 transcriptionally regulates its target gene NDRG1. Luciferase reporter assays showed that NDRG1-OT1 decreased NDRG1 promoter activities. Mass spectrometry, bioinformatics tools, genetic manipulation, and immunoblotting were used to identify the interacting proteins. Surprisingly, different fragments of NDRG1-OT1 had opposite effects on NDRG1. The first quarter fragment (1-149 nt) of NDRG1-OT 1 had no effect on the NDRG1 promoter; the second quarter fragment (150-263 nt) repressed NDRG1 by increasing the binding affinity of HNRNPA1; the third quarter fragment (264-392 nt) improved NDRG1 promoter activity by recruiting HIF-1α; the fourth quarter fragment (393-508 nt) down-regulated NDRG1 promoter activity via down-regulation of KHSRP under hypoxia. In summary, we have found a novel mechanism by which different fragments of the same lncRNA can cause opposite effects within the same target gene.

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Significance of Selective Protein Degradation in the Development of Novel Targeted Drugs and Its Implications in Cancer Therapy

Yang

Wang

Feng

et al. 2020

Advanced Therapeutics

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The evolution of traditional chemotherapeutic drugs to targeted drugs has led to major changes in cancer treatment. However, it remains difficult to develop effective targeted drugs that can act against “undruggable” proteins, including some well‐known oncoproteins such as KRas. Moreover, mutations of target genes limit the use of targeted drugs. Although some strategies such as RNA interference and DNA editing have been adopted to solve these problems, their clinical use remains challenging. Therefore, new strategies are urgently needed to meet the dilemmas encountered in the use of targeted drugs. As protein degradation is a rapid and well‐regulated biological process in cells, targeting protein degradation by inducing cellular protein degradation machinery, regardless of the status of the target, is an attractive idea for developing novel targeted drugs. This review summarizes recent advances in targeted protein degradation, with a focus on the current reagents and strategies used for inducing selective degradation of target proteins to provide clues for the development of novel anticancer drugs and cancer therapies.

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The hypoxia-responsive lncRNANDRG-OT1promotes NDRG1 degradation via ubiquitin-mediated proteolysis in breast cancer cells

Cited by 34 publications

References 37 publications

Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Different effects of long noncoding RNANDRG1-OT1fragments onNDRG1transcription in breast cancer cells under hypoxia

Significance of Selective Protein Degradation in the Development of Novel Targeted Drugs and Its Implications in Cancer Therapy

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