Human satellite III long noncoding RNA imparts survival benefits to cancer cells

Chatterjee, Manjima; Sengupta, Suman

doi:10.1002/cbin.11761

Cited by 5 publications

(10 citation statements)

References 68 publications

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“…This comparison is particularly relevant because of the same tumor type of the analyzed cell lines. Such varying levels of transcription in similar cancer tissues question the premise of an analogous overexpression behavior for HSat1A ncRNA [ 26 , 63 ] or at least presuppose a more complex regulatory scenario. Other cancer cell lines—HeLa and HepG2—show transcription upregulation, while Caco-2 has lower HSat1A transcription.…”

Section: Resultsmentioning

confidence: 99%

“…By turn, (peri)centromeric transcription has been related with cancer [ 17 , 26 , 51 , 62 , 83 ]. HSat1A transcription was assessed in the same cell lines used for copy number analysis, yet with even more dissimilar results.…”

Section: Discussionmentioning

confidence: 99%

“…Many ncRNAs are transcriptionally dysregulated in disease states: in transcript levels [ 25 ] and potentially in transcript processing, or both. Increased satDNA expression has been related with genomic instability [ 26 ]. While preserving chromosome integrity [ 27 – 29 ], tandem repeats can potentially represent beacons of instability in cancer genomes [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…Centromeric αSat (alpha satellite) transcripts in particular have been considered vital for kinetochore stabilization and centromere cohesion [ 38 – 41 ]. The progressive description of pericentromeric HSat2 and HSat3 transcripts has elevated their status to essential in several cellular contexts [ 42 ], like the formation and regulation of heterochromatin [ 43 , 44 ], aging [ 18 , 45 ], response to stress [ 19 , 46 , 47 ], differentiation [ 48 , 49 ], and cancer [ 26 , 50 , 51 ].…”

Section: Introductionmentioning

confidence: 99%

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Human Satellite 1A analysis provides evidence of pericentromeric transcription

et al. 2023

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Background Pericentromeric regions of human chromosomes are composed of tandem-repeated and highly organized sequences named satellite DNAs. Human classical satellite DNAs are classified into three families named HSat1, HSat2, and HSat3, which have historically posed a challenge for the assembly of the human reference genome where they are misrepresented due to their repetitive nature. Although being known for a long time as the most AT-rich fraction of the human genome, classical satellite HSat1A has been disregarded in genomic and transcriptional studies, falling behind other human satellites in terms of functional knowledge. Here, we aim to characterize and provide an understanding on the biological relevance of HSat1A. Results The path followed herein trails with HSat1A isolation and cloning, followed by in silico analysis. Monomer copy number and expression data was obtained in a wide variety of human cell lines, with greatly varying profiles in tumoral/non-tumoral samples. HSat1A was mapped in human chromosomes and applied in in situ transcriptional assays. Additionally, it was possible to observe the nuclear organization of HSat1A transcripts and further characterize them by 3′ RACE-Seq. Size-varying polyadenylated HSat1A transcripts were detected, which possibly accounts for the intricate regulation of alternative polyadenylation. Conclusion As far as we know, this work pioneers HSat1A transcription studies. With the emergence of new human genome assemblies, acrocentric pericentromeres are becoming relevant characters in disease and other biological contexts. HSat1A sequences and associated noncoding RNAs will most certainly prove significant in the future of HSat research.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human Satellite 1A analysis provides evidence of pericentromeric transcription

et al. 2023

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“…It is now clear that HSATIII can be (over)expressed as so-called long noncoding RNAs (lncRNA) in cancer cells [ 77 , 78 ]. Even the primary influence of lncRNA derived from HSATIII on cancer outcomes have been recently described [ 79 ]. Furthermore, in mice, heterochromatic repeats (including alpha-satellites) are transcribed for normal cell function [ 80 ].…”

Section: Chromosomal Heteromorphisms (Chs) and Cancermentioning

confidence: 99%

Chromosomal Heteromorphisms and Cancer Susceptibility Revisited

Liehr

2022

Cells

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Chromosomal heteromorphisms (CHs) are a part of genetic variation in man. The past literature largely posited whether CHs could be correlated with the development of malignancies. While this possibility seemed closed by end of the 1990s, recent data have raised the question again on the potential influences of repetitive DNA elements, the main components of CHs, in cancer susceptibility. Such new evidence for a potential role of CHs in cancer can be found in the following observations: (i) amplification and/or epigenetic alterations of CHs are routinely reported in tumors; (ii) the expression of CH-derived RNA in embryonal and other cells under stress, including cancer cells; (iii) the expression of parts of CH-DNA as long noncoding RNAs; plus (iv) theories that suggest a possible application of the “two-hit model” for euchromatic copy number variants (CNVs). Herein, these points are discussed in detail, which leads to the conclusion that CHs are by far not given sufficient consideration in routine cytogenetic analysis, e.g., leukemias and lymphomas, and need more attention in future research settings including solid tumors. This heightened focus may only be achieved by approaches other than standard sequencing or chromosomal microarrays, as these techniques are at a minimum impaired in their ability to detect, if not blind to, (highly) repetitive DNA sequences.

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A Gene Encoding an Architectural RNA,hsrω, is a Host Genetic Modifier of Cancer Progression inDrosophila

Bajpai

Kundu

et al. 2021

Preprint

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Cells incurring oncogenic hits are often eliminated by cell death via built-in anti-cancer defense mechanisms, broadly termed as intrinsic tumor suppression (ITS). Identification of genetic modifiers of ITS-induced cell death would provide better understanding of inherent tumor-resistance and/or susceptibility. Using a Drosophila model of loss of a tumor suppressor-mediated epithelial tumorigenesis, here we show that perturbations in levels of stress-responsive nuclear long non-coding RNA (lncRNA) hsrω gene, promote epithelial tumorigenesis. Thus, while somatic clones with loss of a tumor suppressor, Lgl, are eliminated by JNK-induced cell death, lgl mutant somatic clones induced either in an hsrω loss-of-function heterozygous genetic background, or upon cell autonomous up- or down-regulation of hsrω in lgl somatic clones, override the JNK-mediated cell death and progress to full blown tumors. These tumors display deregulation of Hippo pathway as seen from a gain of downstream target of inhibition, Diap1, an inhibitor of cell death. We finally show that downregulation in sat III non-coding RNA, a functional analog of hsrω in humans, increases sensitivity of cancer cells to cytotoxic stress-induced cell death. lncRNA hsrω, therefore, constitutes a novel genetic modifier of ITS in Drosophila and of stress-induced cell death in human cancers.SummaryA long non-coding RNA, hsrω, is a novel regulator of JNK-mediated intrinsic tumor suppression in Drosophila.Highlightslgl clones induced in hsrω heterozygous loss-of-function genetic background escape intrinsic tumor suppression (ITS).Perturbation of hsrω in lgl mutant clones, too, leads to their escape from ITS.hsrω homeostasis required for JNK-dependent ITS.Human sat III, a functional analog of hsrω, confers stress-resistant to human cancer cells.

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Human satellite III long noncoding RNA imparts survival benefits to cancer cells

Cited by 5 publications

References 68 publications

Human Satellite 1A analysis provides evidence of pericentromeric transcription

Human Satellite 1A analysis provides evidence of pericentromeric transcription

Chromosomal Heteromorphisms and Cancer Susceptibility Revisited

A Gene Encoding an Architectural RNA,hsrω, is a Host Genetic Modifier of Cancer Progression inDrosophila

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