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The guardians of the genome (p53, TA-p73, and TA-p63) are regulators of tumor suppressor miRNAs network

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Abstract

The tumor suppressor p53 homologues, TA-p73, and p63 have been shown to function as tumor suppressors. However, how they function as tumor suppressors remains elusive. Here, I propose a number of tumor suppressor pathways that illustrate how the TA-p73 and p63 could function as negative regulators of invasion, metastasis, and cancer stem cells (CSCs) proliferation. Furthermore, I provide molecular insights into how TA-p73 and p63 could function as tumor suppressors. Remarkably, the guardians—p53, p73, and p63—of the genome are in control of most of the known tumor suppressor miRNAs, tumor suppressor genes, and metastasis suppressors by suppressing c-myc through miR-145/let-7/miR-34/TRIM32/PTEN/FBXW7. In particular, p53 and TA-p73/p63 appear to upregulate the expression of (1) tumor suppressor miRNAs, such as let-7, miR-34, miR-15/16a, miR-145, miR-29, miR-26, miR-30, and miR-146a; (2) tumor suppressor genes, such as PTEN, RBs, CDKN1a/b/c, and CDKN2a/b/c/d; (3) metastasis suppressors, such as Raf kinase inhibitory protein, CycG2, and DEC2, and thereby they enlarge their tumor suppressor network to inhibit tumorigenesis, invasion, angiogenesis, migration, metastasis, and CSCs proliferation.

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Acknowledgments

Dr. Lakshmanane Boominathan, Ph.D. is the founding Director-cum-senior scientist of the Genome Discovery, Puducherry, India. He devotes this article to his Professors [from the National University of Singapore; The Weizmann Institute of Science; Jawaharlal Institute of Post-graduate Medical Education and Research; Pondicherry Central University, India] who have played a significant role in his career.

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Boominathan, L. The guardians of the genome (p53, TA-p73, and TA-p63) are regulators of tumor suppressor miRNAs network. Cancer Metastasis Rev 29, 613–639 (2010). https://doi.org/10.1007/s10555-010-9257-9

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