ABSTRACT
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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Authorship SSG and MC conceived and designed the experiments; MC performed the experiments; SSG and MC analyzed the results, MC prepared the manuscript; SSG proofread the manuscript.
List of Abbreviations
- LncRNAs
- long non-coding RNAs
- SatIII
- satellite III
- HSF1
- heat shock factor 1
- RNP
- ribonucleoprotein
- nSBs
- nuclear stress bodies
- SF
- splicing factor
- SRp
- serine and arginine-rich protein
- CREBBP
- CREB (cAMP-response element binding protein) binding protein
- hnRNPs
- heterogeneous nuclear RNPs
- HSR
- heat shock response
- HSPs
- heat shock proteins
- HOTAIR
- HOX transcript antisense RNA
- HOX
- homeobox gene
- MALAT1
- metastasis associated lung adenocarcinoma transcript 1
- PANDA
- P21-associated ncRNA DNA damage-activated
- PVT1
- plasmacytoma variant translocation 1
- GAS5
- growth arrest specific 5
- MEG3
- maternally expressed 3
- TonEBP
- tonicity enhancer-binding protein
- CDKs
- cyclin-dependent kinases
- 5-FU
- 5-fluorouracil
- cisplatin
- (cis-Diamminedichloroplatinum (II): CDDP)
- DMEM
- Dulbecco’s modified Eagle’s medium
- RPMI
- Roswell Park Memorial Institute medium
- FBS
- fetal bovine serum
- FISH
- fluorescence in situ hybridization
- shRNA, MTT
- 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
- DMSO
- dimethyl sulfoxide
- NEAT1
- nuclear paraspeckle assembly transcript 1
- SWI/SNF
- SWItch/Sucrose Non-Fermentable
- BRD4
- bromodomain-containing protein 4
- UCA1
- urothelial carcinoma-associated 1
- PI3K/Akt
- phosphatidylinositol-3-kinase/protein kinase B
- NF-κB
- nuclear factor-κB.