Long non‐coding RNA NEAT1 is a transcriptional target of p53 and modulates p53‐induced transactivation and tumor‐suppressor function

Abstract

p53 is one of the most important tumor suppressor genes, and the direct transcriptional targets of p53 must be explored to elucidate its functional mechanisms. Thus far, the p53 targets that have been primarily studied are protein-coding genes. Our previous study revealed that several long non-coding RNAs (lncRNAs) are direct transcriptional targets of p53, and knockdown of specific lncRNAs modulates p53-induced apoptosis. In this study, analysis of next-generation chromatin immunoprecipitation-sequencing (ChIP-seq) data for p53 revealed that the lncRNA NEAT1 is a direct transcriptional target of p53. The suppression of NEAT1 induction by p53 attenuates the inhibitory effect of p53 on cancer cell growth and also modulates gene transactivation, including that of many lncRNAs. Furthermore, low expression of NEAT1 is related to poor prognosis in several cancers. These results indicate that the induction of NEAT1 expression contributes to the tumor-suppressor function of p53 and suggest that p53 and NEAT1 constitute a transcriptional network contributing to various biological functions and tumor suppression.

lncRNA FAM83H‑AS1 is associated with the prognosis of colorectal carcinoma and promotes cell proliferation by targeting the Notch signaling pathway

“…Currently, accumulating lncRNAs have been identified in different biological processes, in which they act as critical regulators in both physiology and pathology, including tumorigenesis. Idogawa et al (26) reported that lncRNA NEAT1 was a transcriptional target of p53 and modulated p53-induced transactivation and tumor-suppressor function. Zhao et al (27) revealed that SNHG5/miR-32 axis regulated cell proliferation and migration of gastric cancer by targeting KLF4.…”

Long Non-Coding RNA (LncRNA) HOXA11-AS Promotes Breast Cancer Invasion and Metastasis by Regulating Epithelial-Mesenchymal Transition

“…According to the site of lncRNA in the genome, it can be classified into 5 types: sense lncRNA, antisense lncRNA, bidirectional lncRNA, intronic lncRNA, and intergenic lncRNA [5]. The main functions of lncRNA include: (1) transcribing and interfering, (2) participating in chromosome rearrangement and histone modification, (3) modifying alternative splicing sequence, and (4) stabilizing mRNA [6]. lncRNA can regulate gene expression at the transcriptional level, post-transcriptional level, and epigenetic level, thus participating in the occurrence and development of tumors [7].…”

lncRNA SNHG5 is associated with poor prognosis of bladder cancer and promotes bladder cancer cell proliferation through targeting p27

“…Accumulating documents have revealed that lncRNAs play a critical role in tumorigenesis and can be used as biomarkers for diagnosis or prediction of survival and recurrence in multiple cancers (5)(6)(7)(8)(9). For instance, in 2017, Idogawa et al reported that long non-coding RNA NEAT1 was a transcriptional target of p53 and modulated p53-induced transactivation and tumor-suppressor function (10). Zhou et al demonstrated that downregulation of lncRNA MEG3 mediated by DNMT3b contributed to nickel malignant transformation of human bronchial epithelial cells via modulating PHLPP1 transcription and HIF-1α translation (11).…”