Limits...
The microRNA feedback regulation of p63 in cancer progression.

Lin C, Li X, Zhang Y, Guo Y, Zhou J, Gao K, Dai J, Hu G, Lv L, Du J, Zhang Y - Oncotarget (2015)

Bottom Line: Remarkably, these data revealed 63 microRNAs that targeted p63.Furthermore, there were 39 microRNAs targeting p63 that were predicted to be regulated by p63.These analyses suggest a crosstalk between p63 and microRNAs.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

ABSTRACT
The transcription factor p63 is a member of the p53 gene family that plays a complex role in cancer due to its involvement in epithelial differentiation, cell cycle arrest and apoptosis. MicroRNAs are a class of small, non-coding RNAs with an important regulatory role in various cellular processes, as well as in the development and progression of cancer. A number of microRNAs have been shown to function as transcriptional targets of p63. Conversely, microRNAs also can modulate the expression and activity of p63. However, the p63-microRNA regulatory circuit has not been addressed in depth so far. Here, computational genomic analysis was performed using miRtarBase, Targetscan, microRNA.ORG, DIANA-MICROT, RNA22-HSA and miRDB to analyze miRNA binding to the 3'UTR of p63. JASPAR (profile score threshold 80%) and TFSEARCH datasets were used to search transcriptional start sites for p53/p63 response elements. Remarkably, these data revealed 63 microRNAs that targeted p63. Furthermore, there were 39 microRNAs targeting p63 that were predicted to be regulated by p63. These analyses suggest a crosstalk between p63 and microRNAs. Here, we discuss the crosstalk between p63 and the microRNA network, and the role of their interactions in cancer.

No MeSH data available.


Related in: MedlinePlus

The human p63 splicing isoformsThe human p63 splicing isoforms. (A) Schematic representation of intron/exon structure of the human p63 gene. The p63 gene has two promoters with the P1 promoter coding for TA (transactivation) isoforms and the P2 promoter coding for N-terminally truncated (ΔN) isoforms. Introns are depicted in white, while exons are colored according to the functional domains (see B). P63 genes express three splice variants and contain different internal promoters. (B) Schematic representation of the human p63 protein splicing variants. Various human p63 variants encoded by the p63 gene with indicated amino acid identity above the TA, DNA binding and oligomerization domain. TAD, Transactivation domain; ΔN, N-terminally truncated variants; Oligo, Oligomerization domain; SAM, Sterile alpha motif.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496160&req=5

Figure 1: The human p63 splicing isoformsThe human p63 splicing isoforms. (A) Schematic representation of intron/exon structure of the human p63 gene. The p63 gene has two promoters with the P1 promoter coding for TA (transactivation) isoforms and the P2 promoter coding for N-terminally truncated (ΔN) isoforms. Introns are depicted in white, while exons are colored according to the functional domains (see B). P63 genes express three splice variants and contain different internal promoters. (B) Schematic representation of the human p63 protein splicing variants. Various human p63 variants encoded by the p63 gene with indicated amino acid identity above the TA, DNA binding and oligomerization domain. TAD, Transactivation domain; ΔN, N-terminally truncated variants; Oligo, Oligomerization domain; SAM, Sterile alpha motif.

Mentions: P63 is a member of the p53 gene family of transcription factors [6, 7]. Like other members of the p53 family [8], the p63 gene generates multiple protein isoforms with distinct properties from two distinct promoters [9]. The transcription of promoter 1, located upstream of exon 1, results in the expression of p63 transcripts containing the N-terminal transactivation domain (TA isoform). Alternatively, transcription from promoter 2, located in an intron, generates p63 transcripts with an N-terminal truncated isoform (ΔN isoform) (Figure 1A) [10]. Moreover, both TAp63 and ΔNp63 can be alternatively spliced at the C-terminal sequence to generate three isoforms named α, β and γ (Figure 1B) [11]. TAp63 is related to cell-cycle arrest and apoptosis and, similar to p53 [12], low levels of TAp63 are detected in various types of cancer tissues [13, 14]. Conversely, ΔNp63 has been implicated in cell proliferation and cell adhesion [15, 16], and this isoform is usually overexpressed in tumor tissues [17–19]. Thus, p63 exhibits isoform-specific expression and functions in human cancer [20, 21].


The microRNA feedback regulation of p63 in cancer progression.

Lin C, Li X, Zhang Y, Guo Y, Zhou J, Gao K, Dai J, Hu G, Lv L, Du J, Zhang Y - Oncotarget (2015)

The human p63 splicing isoformsThe human p63 splicing isoforms. (A) Schematic representation of intron/exon structure of the human p63 gene. The p63 gene has two promoters with the P1 promoter coding for TA (transactivation) isoforms and the P2 promoter coding for N-terminally truncated (ΔN) isoforms. Introns are depicted in white, while exons are colored according to the functional domains (see B). P63 genes express three splice variants and contain different internal promoters. (B) Schematic representation of the human p63 protein splicing variants. Various human p63 variants encoded by the p63 gene with indicated amino acid identity above the TA, DNA binding and oligomerization domain. TAD, Transactivation domain; ΔN, N-terminally truncated variants; Oligo, Oligomerization domain; SAM, Sterile alpha motif.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496160&req=5

Figure 1: The human p63 splicing isoformsThe human p63 splicing isoforms. (A) Schematic representation of intron/exon structure of the human p63 gene. The p63 gene has two promoters with the P1 promoter coding for TA (transactivation) isoforms and the P2 promoter coding for N-terminally truncated (ΔN) isoforms. Introns are depicted in white, while exons are colored according to the functional domains (see B). P63 genes express three splice variants and contain different internal promoters. (B) Schematic representation of the human p63 protein splicing variants. Various human p63 variants encoded by the p63 gene with indicated amino acid identity above the TA, DNA binding and oligomerization domain. TAD, Transactivation domain; ΔN, N-terminally truncated variants; Oligo, Oligomerization domain; SAM, Sterile alpha motif.
Mentions: P63 is a member of the p53 gene family of transcription factors [6, 7]. Like other members of the p53 family [8], the p63 gene generates multiple protein isoforms with distinct properties from two distinct promoters [9]. The transcription of promoter 1, located upstream of exon 1, results in the expression of p63 transcripts containing the N-terminal transactivation domain (TA isoform). Alternatively, transcription from promoter 2, located in an intron, generates p63 transcripts with an N-terminal truncated isoform (ΔN isoform) (Figure 1A) [10]. Moreover, both TAp63 and ΔNp63 can be alternatively spliced at the C-terminal sequence to generate three isoforms named α, β and γ (Figure 1B) [11]. TAp63 is related to cell-cycle arrest and apoptosis and, similar to p53 [12], low levels of TAp63 are detected in various types of cancer tissues [13, 14]. Conversely, ΔNp63 has been implicated in cell proliferation and cell adhesion [15, 16], and this isoform is usually overexpressed in tumor tissues [17–19]. Thus, p63 exhibits isoform-specific expression and functions in human cancer [20, 21].

Bottom Line: Remarkably, these data revealed 63 microRNAs that targeted p63.Furthermore, there were 39 microRNAs targeting p63 that were predicted to be regulated by p63.These analyses suggest a crosstalk between p63 and microRNAs.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

ABSTRACT
The transcription factor p63 is a member of the p53 gene family that plays a complex role in cancer due to its involvement in epithelial differentiation, cell cycle arrest and apoptosis. MicroRNAs are a class of small, non-coding RNAs with an important regulatory role in various cellular processes, as well as in the development and progression of cancer. A number of microRNAs have been shown to function as transcriptional targets of p63. Conversely, microRNAs also can modulate the expression and activity of p63. However, the p63-microRNA regulatory circuit has not been addressed in depth so far. Here, computational genomic analysis was performed using miRtarBase, Targetscan, microRNA.ORG, DIANA-MICROT, RNA22-HSA and miRDB to analyze miRNA binding to the 3'UTR of p63. JASPAR (profile score threshold 80%) and TFSEARCH datasets were used to search transcriptional start sites for p53/p63 response elements. Remarkably, these data revealed 63 microRNAs that targeted p63. Furthermore, there were 39 microRNAs targeting p63 that were predicted to be regulated by p63. These analyses suggest a crosstalk between p63 and microRNAs. Here, we discuss the crosstalk between p63 and the microRNA network, and the role of their interactions in cancer.

No MeSH data available.


Related in: MedlinePlus