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Review
. 2020 Jun 22:10:82.
doi: 10.1186/s13578-020-00445-9. eCollection 2020.

An update on long intergenic noncoding RNA p21: a regulatory molecule with various significant functions in cancer

Roya Amirinejad  1 , Mina Rezaei  2 , Zeinab Shirvani-Farsani  2
Affiliations
Review

An update on long intergenic noncoding RNA p21: a regulatory molecule with various significant functions in cancer

Roya Amirinejad et al. Cell Biosci. .

Abstract

Long intergenic noncoding RNA p21 was mapped on the human chromosome 6p21.2. Accordingly, it was firstly described by promoting the p53-dependent apoptosis in the mouse. Also, it is a new lncRNA playing some vital roles in the cell cycle, apoptosis, cell proliferation, tumorigenesis, invasion, metastasis, and angiogenesis. In this regard, it was shown that, lincRNA-p21 regulates these biological processes involved in carcinogenesis through various signaling pathways including Notch signaling, JAK2/STAT3, and AKT/mTOR pathways. Another mechanism by that lincRNA-p21 can affect these processes is a cross-talk with different miRNAs. In vitro and in vivo studies revealed dysregulation of lincRNA-p21 in various human cancers. In addition, emerging evidence demonstrated that, lincRNA-p21 can be considered as a potential prognostic and therapeutic biomarker in cancers. Also, lincRNA-p21 enhances the response to radiotherapy for colorectal cancer. However, the molecular mechanisms of lincRNA-p21 in carcinogenesis have not been fully elucidated so far. So, this review summarizes the function of lincRNA-p21, as a tumor suppressor factor in different biological processes implicated in cancers.

Keywords: Angiogenesis; Apoptosis; Biomarker; Metastasis; lincRNA-p21; miRNAs.

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Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
LincRNA-p21-induced apoptosis via ING1B and p53. MDM2 monoubiquitinates p53, which leads to its degradation by the proteasome complex. Consequently, the apoptosis genes are inhibited and cell survival genes are activated, resulting in the inhibition of apoptosis (up). On the other hand, ING1b leads to the overexpression of lincRNA-p21. Then, lincRNA-p21 binds to MDM2 and detaches it from p53, which results in the increased p53 stability, the induced apoptosis genes, and the suppressed survival cell genes (down)
Fig. 2
Fig. 2
Cross-talk between lincRNA-p21 and STAT3. a The reduced expression of lincRNA-p21 inhibits its interaction to STAT3, thus promotes the STAT3 transcriptional activity and induces tumor progression. b Overexpression of lincRNA-p21 represses the regulatory activity STAT3 and also inhibits tumorigenesis
Fig. 3
Fig. 3
The role of lincRNA-p21 in invasion and metastasis. Down-regulation of lincRNA-p21 leads to enhance MMP2, MMP9, and miRNA-9 expression, as well as reducing the E-cadherin expression and cell adhesion, which finally promotes invasion and metastasis
Fig. 4
Fig. 4
LincRNA-p21 inhibits Wnt/β-catenin pathway. a miR-17-5p activates Wnt through down-regulating WIF1. bLincRNA-p21 suppresses miR-17-5p leading to the inactivation of Wnt. cLincRNA-p21 down-regulates the β-catenin and inhibits Wnt. WIF1: Wnt inhibitory factor 1
Fig. 5
Fig. 5
The interplay between lincRNA-p21 and miRNAs for the regulation of various biological processes involved in cancer
See this image and copyright information in PMC

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