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

Transcriptional Regulation of miRNAs by p63The diagram illustrates a simple schematic to highlight points of transcriptional regulation of miRNAs by p63. It illustrates that the p63 could modulate the expression of miRNAs by directly or alternative indirectly mechanisms.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Transcriptional Regulation of miRNAs by p63The diagram illustrates a simple schematic to highlight points of transcriptional regulation of miRNAs by p63. It illustrates that the p63 could modulate the expression of miRNAs by directly or alternative indirectly mechanisms.

Mentions: Furthermore, p63 can control the expression of miRNAs by regulating the expression of miRNA transcription factors, as well as several key regulatory factors that allow for the correct maturation of primary miRNA. As an example of the former, the gene of the transcription factor early growth response 2 (EGR2) contains a p63 RE and is therefore a direct target of p63 [106]. Interestingly, it has recently been shown that EGR2 can bind to the pre-miR-142–3p promoter to regulate its expression [107]. Thus, it is plausible that p63 could regulate the expression of miR-142–3p through EGR2. Runt-related transcription factor 1 (RUNX1) has been identified as a direct target of p63 transcriptional regulation [108], and this transcription factor can regulate miR-424 expression [109]. Altogether, these findings suggest that p63 can promote the expression of miR-142–3p by regulating the transcription of RUNX1. Recently, the Drosha gene promoter has been shown to be a target of the NFκB transcription factor [110]. Another study showed that TAp63 can regulate NF-κB transcription and protein stability [111]. These data suggest that p63, by regulating the transcription of NF-κB, can promote the association between Drosha and pri-miRNAs. Moreover, it is reported that p-ΔNp63a is necessary to induce gene promoters for microRNAs (630 and 885–3p), together with certain transcriptional coactivators (e.g., CARM1, KAT2B, TFAP2A). Additionally, p-ΔNp63a, together with transcriptional corepressors (e.g., EZH2, CTBP1, HDACs), is needed to repress promoters for microRNAs (181a-5p, 374a-5p and 519a-3p) in SCC cells exposed to cisplatin [96]. These data suggest that p63, by regulating the transcription of miRNAs, plays important roles in various cancers (Figure 2). The miRNAs demonstrated to be regulated by p63 are summarized in Table 1.


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)

Transcriptional Regulation of miRNAs by p63The diagram illustrates a simple schematic to highlight points of transcriptional regulation of miRNAs by p63. It illustrates that the p63 could modulate the expression of miRNAs by directly or alternative indirectly mechanisms.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Transcriptional Regulation of miRNAs by p63The diagram illustrates a simple schematic to highlight points of transcriptional regulation of miRNAs by p63. It illustrates that the p63 could modulate the expression of miRNAs by directly or alternative indirectly mechanisms.
Mentions: Furthermore, p63 can control the expression of miRNAs by regulating the expression of miRNA transcription factors, as well as several key regulatory factors that allow for the correct maturation of primary miRNA. As an example of the former, the gene of the transcription factor early growth response 2 (EGR2) contains a p63 RE and is therefore a direct target of p63 [106]. Interestingly, it has recently been shown that EGR2 can bind to the pre-miR-142–3p promoter to regulate its expression [107]. Thus, it is plausible that p63 could regulate the expression of miR-142–3p through EGR2. Runt-related transcription factor 1 (RUNX1) has been identified as a direct target of p63 transcriptional regulation [108], and this transcription factor can regulate miR-424 expression [109]. Altogether, these findings suggest that p63 can promote the expression of miR-142–3p by regulating the transcription of RUNX1. Recently, the Drosha gene promoter has been shown to be a target of the NFκB transcription factor [110]. Another study showed that TAp63 can regulate NF-κB transcription and protein stability [111]. These data suggest that p63, by regulating the transcription of NF-κB, can promote the association between Drosha and pri-miRNAs. Moreover, it is reported that p-ΔNp63a is necessary to induce gene promoters for microRNAs (630 and 885–3p), together with certain transcriptional coactivators (e.g., CARM1, KAT2B, TFAP2A). Additionally, p-ΔNp63a, together with transcriptional corepressors (e.g., EZH2, CTBP1, HDACs), is needed to repress promoters for microRNAs (181a-5p, 374a-5p and 519a-3p) in SCC cells exposed to cisplatin [96]. These data suggest that p63, by regulating the transcription of miRNAs, plays important roles in various cancers (Figure 2). The miRNAs demonstrated to be regulated by p63 are summarized in Table 1.

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