Investigating DNA-damage responsive long non-coding RNA (lncRNA)

The human genome is routinely subject to endogenous (e.g. oxidative stress) and exogenous (e.g. radiation, UV) factors that induce DNA lesions. These lesions may accumulate and impair cell function or cause cancer. Hence, DNA damage repair and preservation are prerequisites for normal cellular function and maintaining genome integrity. Current research suggests that long non-coding RNAs (lncRNA) play a role in DNA damage response (DDR). lncRNAs are RNA transcripts >200 nt that do not code for proteins. After transcription, they interact with DNA, protein, mRNA, or other non-coding RNA to influence gene expression and protein function. However, there is a lack of research concerning the role of lncRNA in DDR. This study aimed to investigate and quantify the expression of DNA-damage-responsive lncRNAs in a time-course experiment. To do so, human embryonic kidney 293T (HEK293T) cells were exposed to ionizing radiation (IR) at 2 Gy to induce 60-100 double-stranded breaks (DSB) per cell. Following this exposure, RNA was collected at 4 different time points (1, 4, 8, and 24 hrs). Finally, Real-time Quantitative PCR was performed to quantify the expression of select lncRNA genes. Our findings demonstrate an association between DDR and lncRNA gene expression. We found a temporal upregulation or downregulation of lncRNA genes, specifically ENSG00000250519, ENSG00000231595, ENSG00000254338, and ENSG00000223749. The influence of DNA lesions on the expression of these lncRNA increased over 24 hrs. This finding asserts that lncRNA is an epigenetic regulator that may influence signalling networks related to DNA damage. Hence, lncRNAs may serve as biomarkers for the diagnosis, treatment, and prognosis of cancer and other diseases.