A high-throughput screen identifies the long non-coding RNA DRAIC as a regulator of autophagy.
Imke TiessenMarie H AbildgaardMichal LubasHelene M GyllingCornelia SteinhauerElin J PietrasSven DiederichsLisa B FrankelAnders Henrik LundPublished in: Oncogene (2019)
Autophagy is a conserved degradation process that occurs in all eukaryotic cells and its dysfunction has been associated with various diseases including cancer. While a number of large-scale attempts have recently identified new molecular players in autophagy regulation, including proteins and microRNAs, little is known regarding the function of long non-coding RNAs (lncRNAs) in the regulation of this process. To identify new long non-coding RNAs with functional implications in autophagy, we performed a high-throughput RNAi screen targeting more than 600 lncRNA transcripts and monitored their effects on autophagy in MCF-7 cells. We identified 63 lncRNAs that affected GFP-LC3B puncta numbers significantly. We validated the strongest hit, the lncRNA DRAIC previously shown to impact cell proliferation, and revealed a novel role for this lncRNA in the regulation of autophagic flux. Interestingly, we find DRAIC's pro-proliferative effects to be autophagy-independent. This study serves as a valuable resource for researchers from both the lncRNA and autophagy fields as it advances the current understanding of autophagy regulation by non-coding RNAs.
Keyphrases
- long non coding rna
- cell death
- endoplasmic reticulum stress
- poor prognosis
- high throughput
- induced apoptosis
- oxidative stress
- signaling pathway
- cell cycle arrest
- single cell
- squamous cell carcinoma
- gene expression
- transcription factor
- pi k akt
- mass spectrometry
- papillary thyroid
- high resolution
- dna methylation
- genome wide analysis