Neat-en-ing up our understanding of p53 pathways in tumor suppression

Figures & data

Table 1. LincRNAs directly regulated by p53 with functions potentially relevant to p53-mediated tumor suppression

Name	Reported function	Ref.
PANDA	Interacts with NF-YA to inhibit the expression of pro-apoptotic genes upon DNA damage and promote cell survival.	[9]
NEAT1	Suppresses cellular transformation in oncogene-expressing fibroblasts and in the pancreas by enforcing the expression of differentiation genes. It can enhance cell proliferation, cell survival, cell invasion and EMT in some cancer cell lines. Finally, it can promote ATR signaling upon replication stress, preventing the accumulation of DNA damage.	[24,25,48,50–55]
PINCR	Interacts with Matrin 3, inducing cell cycle arrest and cell survival upon DNA damage in human colorectal cancer cells.	[14]
TUG1	Interacts with PRC2 and represses HOXB7, decreasing cell proliferation in non-small cell lung cancer.	[15,16]
PVT1	The PVT1 locus contains the lincRNA PVT1 and different microRNAs, including miR-1204, which was shown to have antiproliferative effects and to trigger apoptosis through the increase of p53 levels. PVT1 was also shown to promote cell survival.	[11,12]
lincRNA-p21	Interacts with hnRNP-K to act as a global mediator of p53-dependent repression and is required for cell cycle arrest and apoptosis induction in response to DNA damage.	[7,8]
DINO	Enhances p53 stabilization upon DNA damage.	[19]
PURPL	Destabilizes p53 under basal conditions.	[20]
PR-lncRNA-1,10	Act to facilitate p53 binding to target genes, promoting cell cycle arrest and inducing cell death upon DNA damage.	[13]
PINT	Interacts with PRC2 to inhibit proliferation in human cells. In mouse cells, promotes proliferation and survival.	[10]
Loc285194	Inhibits miR-211 to limit proliferation of colorectal and breast cancer cell lines in vitro. It also dampens subcutaneous tumor growth of colorectal cancer cells.	[21]
LED	Binds and activates strong enhancers, supporting the p53 transcriptional response and inducing cell cycle arrest upon p53 activation.	[17]
TRINGS	Interacts with STRAP and inhibits necrosis upon glucose starvation.	[18]

Figure 1. The role of Neat1 in suppressing transformation in pancreatic cancer

Neat1 blocks the transformation of normal pancreatic acinar and ductal cells into premalignant lesions, namely Pancreatic Intraepithelial Neoplasias (PanINs) and Intraductal Papillary Mucinous Neoplasm (IPMN)-like lesions, respectively. Both premalignant lesions may ultimately develop into malignant pancreatic ductal adenocarcinoma (PDAC).

Figure 2. Mechanisms of Neat1 action

Different molecular mechanisms of action have been proposed for NEAT1. These include: retaining A-to-I edited pre-mRNAs in the nucleus, promoting processing of pre-mRNAs and pri-miRNAs, sequestering proteins into paraspeckles and away from chromatin, and modulating gene expression through direct interactions with chromatin. Interactions with chromatin can result in histone modification and potentially chromatin remodeling events through interactions with proteins from the SWI/SNF complex. In the figure, NEAT1 is represented by a twisted blue line and paraspeckle proteins are represented by red and purple ovals.

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