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A novel molecular mechanism for a long non-coding RNA PCAT92 implicated in prostate cancer

Authors: Bawa P. S.; Ravi S.; Paul S.; Chaudhary B.; Srinivasan S.;

A novel molecular mechanism for a long non-coding RNA PCAT92 implicated in prostate cancer

Abstract

The role of many lncRNAs in cancer remains elusive including that for a Prostate Cancer Associated Transcript 92 (PCAT92). PCAT92 shares the locus on chromosome 13 with ABCC4 gene, known to be implicated in prostate cancer. It has been shown that PCAT92 and ABCC4 are up-regulated in prostate cancer samples from multiple transcriptome datasets. Among the prostate cancer cell-lines LNCaP showed maximum overexpression of PCAT92 compared to control cell-line RWPE-1. We have shown that knockdown of PCAT92 in LNCaP cells reduces cell viability and proliferation and down-regulates ABCC4 transcript/protein expression. The shared region between PCAT92 and ABCC4 has a binding site for an oncogenic transcription factor (ZIC2) which is also upregulated in the majority of datasets studied here. ZIC2 binding to the predicted ABCC4 promoter has been confirmed using pull-down assay. Interestingly, under PCAT92 knockdown condition, there is a reduction in the ZIC2 binding to ABCC4 promoter indicating the potential involvement of PCAT92 in the recruitment of ZIC2. We have identified distinct regions on PCAT92 with potential to bind to ZIC2 non-DNA binding Zinc-finger domain and potential for triplex formation near ABCC4 promoter region, which have been experimentally validated. Together, these observations and localization in the nucleus suggests that PCAT92 may play a role in prostate cancer by increasing the local concentration of ZIC2 by forming RNA-DNA triplex near ABCC4 promoter thus helping in recruitment of ZIC2 for ABCC4 regulation.

Country
Italy
Keywords

ABCC4; lncRNA; PCAT92; Prostate cancer; ZIC2, Research Paper

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
5
Average
Average
Average
Green
gold