Heat Shock Affects Mitotic Segregation of Human Chromosomes Bound to Stress-Induced Satellite III RNAs

Giordano, Manuela; Infantino, Lucia; Biggiogera, Marco; Montecucco, Alessandra; Biamonti, Giuseppe

doi:10.3390/ijms21082812

Cited by 19 publications

(16 citation statements)

References 67 publications

(107 reference statements)

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“…Several studies have emphasized on the transcriptional and epigenetic status of the pericentromeric satellite transcripts that if altered enhances the risk of malignancies (Giordano et al, 2020; Zhu et al, 2018). Since we observed that the level of SatIII expression varies between unstressed and heat‐shocked human colon and breast cancer cells, we further decided to investigate whether SatIII transcripts are required for cancer cell progression.…”

Section: Resultsmentioning

confidence: 99%

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

Chatterjee

Sengupta

2022

Cell Biology International

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Long noncoding RNAs (lncRNAs) are heterogeneous group of transcripts that lack coding potential and have essential roles in gene regulations. Recent days have seen an increasing association of noncoding RNAs with human diseases, especially cancers. One interesting group of noncoding RNAs strongly linked to cancers are heterochromatic repetitive Satellite RNAs. Satellite RNAs are transcribed from pericentromeric heterochromatic region of the human chromosomes. Satellite II RNA, most extensively studied, is upregulated in wide variety of epithelial cancer. Similarly, alpha satellite is over expressed in BRCA1‐deficient tumors. Though much is known about alpha satellites and SatII repeats, little is known about Satellite III (SatIII) lncRNAs in human cancers. SatIII repeats, though transcriptionally silent in normal conditions is actively transcribed under condition of stress, mainly heat shock. In this study, we show that colon and breast cancer cells aberrantly transcribes SatIII, in a heat shock factor I (HSF1)‐independent manner. Our study also reveals that, the overexpression of SatIII RNA favors cancer cell survival by overriding chemo drug‐induced cell death. Interestingly, knockdown of SatIII sensitizes cells toward chemotherapeutic drugs. This sensitization is possibly mediated by restoration of p53 protein expression that facilitates cell death. Heat shock however helps SatIII to continue with its pro‐cell survival function. Our results, therefore suggest SatIII to be an important regulator of human cancers. Induction of SatIII is not only a response to the oncogenic stress but also facilitates cancer progression by a distinct pathway that is different from heat stress pathway.

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Section: Resultsmentioning

confidence: 99%

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

Chatterjee

Sengupta

2022

Cell Biology International

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“…The possibility of polymorphisms affecting the HSEs present on 9q12 or Yq12 themselves is unlikely given the large number of repetitive motifs, thus limiting the impact of a few mutational events at the Yq12 locus. Intriguingly, on the basis of a recent article showing that cis accumulation of SATIII transcripts causes the mis-segregation of the chromosome from which they originate (Giordano et al 2020 ), the expression of SATIII RNAs and formation of primary nSBs on chromosome Y may represent a significant source of instability for this chromosome too. However, while we were able to confirm the large percentage of chromosome lagging affecting chromosome 9 on HeLa cells used as a control, we were not able to detect chromosome instability in H1080 cell line submitted to heat shock followed or not to different time of recovery at 37 °C (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Chromosome Y pericentric heterochromatin is a primary target of HSF1 in male cells

et al. 2021

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The heat shock factor 1 (HSF1)-dependent transcriptional activation of human pericentric heterochromatin in heat-shocked cells is the most striking example of transcriptional activation of heterochromatin. Until now, pericentric heterochromatin of chromosome 9 has been identified as the primary target of HSF1, in both normal and tumor heat-shocked cells. Transcriptional awakening of this large genomic region results in the nuclear accumulation of satellite III (SATIII) noncoding RNAs (ncRNAs) and the formation in cis of specific structures known as nuclear stress bodies (nSBs). Here, we show that, in four different male cell lines, including primary human fibroblasts and amniocytes, pericentric heterochromatin of chromosome Y can also serve as a unique primary site of HSF1-dependent heterochromatin transcriptional activation, production of SATIII ncRNA, and nucleation of nuclear stress bodies (nSBs) upon heat shock. Our observation suggests that the chromosomal origin of SATIII transcripts in cells submitted to heat shock is not a determinant factor as such, but that transcription of SATIII repetitive units or the SATIII ncRNA molecules is the critical element of HSF1-dependent transcription activation of constitutive heterochromatin.

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“…Several studies have emphasized on the transcriptional and epigenetic status of the pericentromeric satellite transcripts that if altered enhances the risk of malignancies Giordano et al, 2020). Since, we observed that the level of SatIII expression varies between unstressed and heat shocked-human colon and breast cancer cells, we further decided to investigate whether SatIII transcripts are required for cancer cell progression.…”

Section: Satiii Transcription Promotes Proliferation Of Hct-15 (Colon) and Zr-75-1 (Breast Cancer) Cellsmentioning

confidence: 99%

Human Satellite III long non-coding RNA imparts survival benefits to cancer cells

Chatterjee

Sengupta

2021

Preprint

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Long non-coding RNAs are heterogeneous group of transcripts that lack coding potential and have crucial roles in gene regulations. Recent days have seen an increasing association of non-coding RNAs with human diseases, especially cancers. Satellite III (SatIII) lncRNAs are transcribed from pericentromeric heterochromatic region of the human chromosome. Though transcriptionally silent in normal conditions, SatIII is actively transcribed under condition of stress, mainly heat shock. SatII repeat, another component of pericentromeric region of human chromosome, has been associated with wide variety of epithelial cancer. Overexpression of Satellite RNAs induces breast cancer in mice. Though much is known about Satellite RNAs, which includes alpha satellites and SatII repeats, however little is known about SatIII in human cancers. Hence we directed our study to understand the role of human Satellite III repeats in cancerous conditions. In the present study, we show that colon and breast cancer cells transcribe SatIII independent of heat shock, in an HSF1-independent manner. Our study also reveals that, overexpression of SatIII RNA favours cancer cell survival by overriding chemo drug-induced cell death. Knockdown of SatIII sensitizes cells towards chemotherapeutic drugs. SatIII transcript knockdown restores the expression of p53 protein, which in turn facilitates cell death. Heat shock however helps SatIII to continue with its pro-cell survival function. Our results, therefore suggest SatIII to be an important regulator of human cancers. Induction of SatIII is not only a response to the oncogenic stress but also facilitates cancer progression by a distinct pathway that is different from heat stress pathway.

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Heat Shock Affects Mitotic Segregation of Human Chromosomes Bound to Stress-Induced Satellite III RNAs

Cited by 19 publications

References 67 publications

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

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

Chromosome Y pericentric heterochromatin is a primary target of HSF1 in male cells

Human Satellite III long non-coding RNA imparts survival benefits to cancer cells

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