title: Tumor FOXP3 represses the expression of long noncoding RNA 7SL.
abstract: The long noncoding RNA 7SL was over-expressed in tumor cells to promote cell growth through repressing translation of P53. However, the regulatory mechanism of 7SL remains to be defined. FOXP3 was identified as a suppressor in several tumors in addition to be a marker of regulatory T cells. In this study, we detected that over-expression of FOXP3 repressed the transcription of 7SL RNA and contributed to inhibiting tumor growth. Knock down of FOXP3 in MCF-10A normal mammary breast cells up-regulated the transcription of 7SL RNA. Chromatin Immuno-precipitation (ChIP) analysis showed that FOXP3 directly bound to the Forkhead/HNF-3 domain DNA binding sites (-789 to -795) relative to the transcription start site. Meanwhile, Luciferase analysis showed that FOXP3 repressed the full-length 7SL promoter activity, but this suppressive effect was reversed after mutation of the FOXP3 binding site. Further studies showed that FOXP3 promoted the expression of P53 at translational levels through repressing 7SL RNA. In conclusion, this study suggests that 7SL RNA is a direct target of FOXP3 and may be involved in the formation of FOXP3/P53 feedback loop.
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China.
authors.forename: Huizhu
authors.initials: H
authors.lastname: Ren
authors.affiliation: Tianjin Key Laboratory of Food Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, 300134, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute of Radiation Medicine of Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, 300192, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 300070 Tianjin, China. Electronic address: chunyanshan15@gmail.com.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Shan
mesh_terms: D045744:Cell Line, Tumor; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D012097:Repressor Proteins
keywords: 7SL; FOXP3; Long noncoding RNA; P53