The Interplay between Noncoding RNAs and p21 Signaling in Gastrointestinal Cancer: From Tumorigenesis to Metastasis

Author:

Rahmani Farzad123,Zandigohar Mehrdad4,Safavi Pegah5,Behzadi Maryam6,Ghorbani Zeynab7,Payazdan Mahya8,Ferns Gordon9,Hassanian Seyed Mahdi23,Avan Amir2310

Affiliation:

1. Department of Clinical Biochemistry, Kashmar School of Nursing, Mashhad University of Medical Sciences, Mashhad, Iran

2. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3. Basic Medical Sciences Institute, Mashhad University of Medical Sciences, Mashhad, Iran

4. Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, Illinois, 60612, USA

5. Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran, Iran

6. Department of Biology, Faculty of Sciences, Shiraz University, Shiraz, Iran

7. Department of Anatomical Science, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

8. Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

9. Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, BN1 9PH, UK

10. Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Abstract: Non-coding RNAs (ncRNAs) are emerging as important regulators in various pathological conditions, including human cancers. NcRNAs exert potentially crucial effects on cell cycle progression, proliferation, and invasion in cancer cells by targeting various cell cycle-related proteins at transcriptional and post-transcriptional levels. As one of the key cell cycle regulatory proteins, p21 is involved in various processes, including the cellular response to DNA damage, cell growth, invasion, metastasis, apoptosis, and senescence. P21 has been shown to have either a tumor-suppressive or oncogenic effect depending on the cellular localization and posttranslational modifications. P21 exerts a significant regulatory effect on both G1/S and G2/M checkpoints by regulating the function of cyclin-dependent kinase enzymes (CDKs) or interacting with proliferating cell nuclear antigen (PCNA). P21 has an important effect on the cellular response to DNA damage by separating DNA replication enzymes from PCNA and inhibiting DNA synthesis resulting in G1 phase arrest. Furthermore, p21 has been shown to negatively regulate the G2/M checkpoint through the inactivation of cyclin-CDK complexes. In response to any cell damage caused by genotoxic agents, p21 exerts its regulatory effects by nuclear preservation of cyclin B1-CDK1 and preventing their activation. Notably, several ncRNAs, including lncRNAs and miRNAs, have been shown to be involved in tumor initiation and progression through the regulation of the p21 signaling axis. In this review, we discuss the miRNA/lncRNA-dependent mechanisms that regulate p21 and their effects on gastrointestinal tumorigenesis. A better understanding of the regulatory effects of ncRNAs on the p21 signaling may help to discover novel therapeutic targets in gastrointestinal cancer.

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery,Pharmacology

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