New insights into the role of non-coding RNAs as transcriptional targets of p53

Abstract

undergoes programmed cell death (6). Th e main role of p53 as a carcinogenic inhibitor consists in the regulation at the transcriptional level of the target genes that control various cellular processes including programmed cell death, DNA repair mechanisms, autophagy, metabolism, cell cycle control and thus genetic integrity (7-10). Th e elements targeted by p53, a cancer suppressor interacting with numerous target genes, were presented through meta-analysis statistics, which showed that the target genes characterized by high confi dence are involved in numerous feedback loops at cellular level such as cell cycle arrest, metabolism, and mRNA translation. At the same time, a series of mechanisms were associated with the modulatory aspects of gene control in response to p53 (11-13). To our knowledge, research studies revealed that p53 can act as a catalyst of transcription. Moreover, gene down-regulation by p53 is indirect and Abstract P53 classifies as one of the main tumor suppressor gene and the identification of its direct transcriptional targets such as certain non-coding RNAs (ncRNAs) is important for understanding the development and progression of cancer. Multiple ncRNAs are targeting p53 and are involved in many cellular processes such as cell cycle arrest, metabolism, apoptosis, autophagy and feedback mechanisms. Also, various ncRNAs were found to modulate p53-dependent gene regulation. These include microRNAs such as miR-660, miR-486, miR-34 and lncRNAs such as nuclear enriched abundant transcript 1 (NEAT1), which contribute to the tumor-suppressor function of the p53 protein. Long intergenic non-coding RNA, LincRNA-p21, has been proclaimed to promote apoptosis while other p53-regulated lncRNAs including PANDA and Pint antagonize p53 activity by limiting the activation of proapoptotic genes. Taking into account the activity of the proapoptotic transcription factor p53, new conclusions point to a new concept of cellular quality control since ncRNAs-based deregulation in cancer functions in the absence of p53 coding sequence mutations.

Biophysical characterisation of human LincRNA-p21 sense and antisense Alu inverted repeats

“…The tumour suppressor protein p53 is an important transcription factor that regulates a variety of cellular processes, including cell-cycle control, DNA repair, apoptosis, senescence, and cellular stress responses through the activation and repression of target genes ( 1 , 2 ). Despite playing a critical role in the DNA damage response, p53’s genome is frequently mutated in cancer cells, exposing a vulnerability in cell cycle regulation ( 3 , 4 ). Nevertheless, when DNA damage occurs, p53 upregulates the expression of genes involved in the cell cycle arrest and DNA repair processes, which leads to cell survival, but also facilitates the initiation of apoptosis for cancerous cells ( 5 ).…”