Reciprocal regulation of chromatin state and architecture by<i>HOTAIRM1</i>contributes to temporal collinear<i>HOXA</i>gene activation

Wang, Xue Q.D.; Dostie, Josée

doi:10.1093/nar/gkw966

Cited by 55 publications

(80 citation statements)

References 52 publications

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“…HOTAIRM1 has 2 transcript variants with 2 or 3 exons, with the first and last exons being shared. This lncRNA seems to undergo alternative splicing, and a previous study reporting on the role of HOTAIRM1 in the regulation of temporal collinear activation of HOXA genes in embryonic stem cells showed the major isoform to be the spliced form with all 3 exons [34]. On the contrary, in our breast cancer model system, we found that the spliced form with exons 1 and 3 was the predominant form.…”

Section: Discussioncontrasting

confidence: 52%

“…On the contrary, in our breast cancer model system, we found that the spliced form with exons 1 and 3 was the predominant form. Similarly, in acute myeloid leukemia (AML), the spliced form containing exons 1 and 3 was shown to be more prominent [34,35]. In both our system and the AML model, the spliced form containing exon 2 could not be detected.…”

Section: Discussionmentioning

confidence: 57%

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The LncRNA HOTAIRM1 Promotes Tamoxifen Resistance by Mediating HOXA1 Expression in ER+ Breast Cancer Cells

Kim¹,

Oh²,

Lee³

et al. 2020

J. Cancer

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Breast cancer is one of the most commonly diagnosed cancers in women worldwide. Approximately 40% of patients with breast cancer acquire endocrine resistance following therapy with tamoxifen. Many explanations for the development of endocrine resistance have been put forward, one of them being the dysregulation of long non-coding RNAs (lncRNAs). The lncRNA HOTAIRM1, known to be involved in myelopoiesis as well as transcriptional regulation of the HOXA genes in embryonic stem cells, is also expressed in breast cancer cells. This study explored the molecular mechanisms of HOTAIRM1 involved in acquired tamoxifen resistance. We showed that HOTAIRM1 and HOXA1 are concurrently up-regulated in tamoxifen-resistant MCF7 (TAMR) cells. Knockdown of HOTAIRM1 down-regulated HOXA1 expression and restored sensitivity to tamoxifen. In addition, the knockdown of HOXA1 showed similar effects, suggesting that the HOTAIRM1/HOXA1 axis regulates tamoxifen resistance. Furthermore, we showed that HOTAIRM1 directly interacts with EZH2 and prevents the PRC2 complex from binding and depositing H3K27me3 on the putative promoter of HOXA1. Together, our findings suggest that HOXA1 and its neighboring lncRNA, HOTAIRM1, might serve as potential therapeutic targets for ER+ breast cancer patients who have acquired tamoxifen resistance.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 57%

The LncRNA HOTAIRM1 Promotes Tamoxifen Resistance by Mediating HOXA1 Expression in ER+ Breast Cancer Cells

Kim¹,

Oh²,

Lee³

et al. 2020

J. Cancer

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“…HOTAIRM1 expression is activated by all-trans retinoic acid, which induces the differentiation of myeloid progenitor cells to granulocytes and mature myeloid cells [53]. HOTAIRM1 transcript also interacts and form complexes with transcripts of other key chromatin structure modulating proteins such as CBX1, PRC1 and PRC2 [242]. HOTAIRM1 was overexpressed in NPM1mutated AML.…”

Section: Clinical Significance Of Ncrnas In Leukemiamentioning

confidence: 99%

Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance

et al. 2020

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Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate. Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets.

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“…HOTAIRM1 lncRNA has been reported to participate in the regulation of multiple biological processes. [ 70,71 ] In myeloid cells, HOTAIRM1 was shown to induce the degradation of promyelocytic‐retinoic acid receptor alpha oncoprotein by promoting the formation of autophagosomes, resulting in the suppression of myeloid cell differentiation in acute promyelocytic leukemia cells. [ 72 ]…”

Section: Reagents Involved In Selective Protein Degradationmentioning

confidence: 99%

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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Reciprocal regulation of chromatin state and architecture byHOTAIRM1contributes to temporal collinearHOXAgene activation

Cited by 55 publications

References 52 publications

The LncRNA HOTAIRM1 Promotes Tamoxifen Resistance by Mediating HOXA1 Expression in ER+ Breast Cancer Cells

The LncRNA HOTAIRM1 Promotes Tamoxifen Resistance by Mediating HOXA1 Expression in ER+ Breast Cancer Cells

Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance

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

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