title: Human Trefoil Factor 3 induces the transcription of its own promoter through STAT3.
abstract: Human trefoil factor 3 (hTFF3) is a small peptide of potential therapeutic value. The mechanisms underlying the transcriptional regulation of hTFF3 remain unclear. The purpose of this study was to identify the core functional elements for the self-induction action of hTFF3 and transcription factors. First, truncated promoters were constructed to identify the functional regions of the hTFF3 promoter. Next, point mutation, chromatin immunoprecipitation, RNA interference, and gene overexpression experiments were performed to analyze the transcriptional binding sites responsible for the self-induced transcription of hTFF3. Our results revealed the -1450 bp to -1400 bp fragment of the hTFF3 promoter was the functional region for the self-induction action of hTFF3. Bioinformatics analysis confirmed that a STAT3 binding site is present in the -1417 bp to -1409 bp region. Subsequently, site-directed mutagenesis analysis determined that this STAT3 binding site was critical for the self-induction effect of hTFF3. ChIP experiments confirmed that STAT3 binds to the hTFF3 promoter. STAT3 overexpression and knockdown experiments revealed that STAT3 enhanced the self-induction effect and the expression of hTFF3. This study confirmed that hTFF3 exhibits self-induction action, and that STAT3 is the key transcription factor to maintain the function of self-induction.
authors.affiliation: Department of Burn Surgery, Huaihai Hospital affiliated to Xuzhou Medical College, Xuzhou 221004, China.|Department of Burn Surgery, No. 97 Hospital of PLA, Xuzhou 221004, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Burn Surgery, Huaihai Hospital affiliated to Xuzhou Medical College, Xuzhou 221004, China.|Department of Burn Surgery, No. 97 Hospital of PLA, Xuzhou 221004, China.
authors.forename: Liangxi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Burn Surgery, Huaihai Hospital affiliated to Xuzhou Medical College, Xuzhou 221004, China.|Department of Burn Surgery, No. 97 Hospital of PLA, Xuzhou 221004, China.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Burn Surgery, Huaihai Hospital affiliated to Xuzhou Medical College, Xuzhou 221004, China.|Department of Burn Surgery, No. 97 Hospital of PLA, Xuzhou 221004, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Burn Surgery, Huaihai Hospital affiliated to Xuzhou Medical College, Xuzhou 221004, China.|Department of Burn Surgery, No. 97 Hospital of PLA, Xuzhou 221004, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Deng
mesh_terms: D020029:Base Pairing / Q000235:genetics; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D000071165:Trefoil Factor-3 / Q000235:genetics*
chemical_list: D050796:STAT3 Transcription Factor; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3