The dichotomy of p53 regulation by noncoding RNAs.
The p53 tumor suppressor gene is the most frequently mutated gene in cancer. Significant progress has been made to discern the importance of p53 in coordinating cellular responses to DNA damage, oncogene activation, and other stresses. Noncoding RNAs are RNA molecules functioning without being translated into proteins. In this work, we discuss the dichotomy of p53 regulation by noncoding RNAs with four unconventional questions. First, is overexpression of microRNAs responsible for p53 inactivation in the absence of p53 mutation? Second, are there somatic mutations in the noncoding regions of the p53 gene? Third, is there a germline mutant in the noncoding regions of the p53 gene that predisposes carriers to cancer? Fourth, can p53 activation mediated by a noncoding RNA mutation cause cancer? This work highlights the prominence of noncoding RNAs in p53 dysregulation and tumorigenesis.
Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY 40202, USA.
Qipan
Q
Deng
Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY 40202, USA.
Lindsey
L
Becker
Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY 40202, USA.
Xiaodong
X
Ma
Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng 475000, China.
Xiaoming
X
Zhong
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ken
K
Young
Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY 40202, USA.
Kenneth
K
Ramos
Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY 40202, USA School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China yong.li@louisville.edu yong.li@outlook.com.
Yong
Y
Li
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics; D022661:RNA, Untranslated / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; D022661:RNA, Untranslated; D016159:Tumor Suppressor Protein p53
3′UTR; activation; mutation; noncoding RNA; p53; polymorphism; ribosomopathies