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Gene expression data from human breast cancer MCF-7 cells treated with siRNAs targeting long non-coding RNA TMPO-AS1

ABSTRACT: Gene expression data from human breast cancer MCF-7 cells treated with siRNAs targeting long non-coding RNA TMPO-AS1

PROVIDER: PRJNA529673 | ENA |

REPOSITORIES: ENA

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Gene expression data from human breast cancer MCF-7 cells treated with siRNAs targeting long non-coding RNA TMPO-AS1

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Transcriptomic analysis by AmpliSeq Ion Torrent to explore the effects of the long non-coding RNA TGFB2-AS1 on gene expression in human keratinocytes

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Project description:HIFA-AS1, an antisense transcript of HIF1α gene, is a 652-bp long non-coding RNA (lncRNA) which globally expressed in multiple tissues of animals. Recent evidence indicated that the HIFA-AS1 was involved in tumorigenesis of several types of cancer, but there were no reports on pancreatic cancer (PC). In order to investigate whether the HIFA-AS1 could mediate the PC or not, it was overexpressed in a PC cell line (PANC-1), and a series of experiments including cell viability detection, flow cytometry, and transwell migration were performed. Functionally, the results indicated that overexpression (OE) of HIFA-AS1 could inhibit proliferation and shift, and promote apoptosis of PC cells. Moreover, to explore underlying molecular mechanism of HIFA-AS1 in PC cells, the iTRAQ (isobaric tags for relative and absolute quantification) quantitative proteomics analysis was implemented. Mechanistically, it was found that OE of HIFA-AS1 globally affected the expression levels of multiple protein associated with metabolism of cancer, suggesting that HIFA-AS1 might regulate the tumorigenesis of PC by up- and down-regulating the gene expression.

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Long non-coding RNA DARS-AS1 promotes tumor progression by suppressing PACT-mediated PKR activation

Project description:Cancer cells evolve various mechanisms to overcome cellular stresses and maintain progression. Protein kinase R (PKR) and its protein activator (PACT) are the initial responders in monitoring diverse stress signals and lead to cell proliferation inhibition and cell apoptosis in consequence. However, the regulation of PACT-PKR pathway in cancer cells is largely unknown. Herein, we identify that the long non-coding RNA (lncRNA) aspartyl-tRNA synthetase antisense RNA 1 (DARS-AS1) is directly involved in the inhibition of the PACT-PKR pathway and promotes cancer cell proliferation. Using large-scale CRISPRi functional screening of 971 cancer-associated lncRNAs, we find that DARS-AS1 is associated with significantly enhanced cancer cell proliferation. Accordingly, knocking down DARS-AS1 inhibits cell proliferation of multiple cancer cell lines and promotes cancer cell apoptosis in vitro and significantly reduces tumor growth in vivo. Mechanistically, DARS-AS1 directly binds to the activator domain of PACT and prevents PACT-PKR interaction, thereby decreasing PKR activation, eIF2α phosphorylation and inhibiting apoptotic cell death. Clinically, DARS-AS1 is broadly expressed across multiple cancers and the increased expression of this lncRNA indicates poor prognosis. This study elucidates the lncRNA DARS-AS1 directed cancer-specific modulation of the PACT-PKR pathway and provides a novel target for cancer prognosis and therapeutic treatment.

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