title: miR-141 is involved in BRD7-mediated cell proliferation and tumor formation through suppression of the PTEN/AKT pathway in nasopharyngeal carcinoma.
abstract: Bromodomain containing 7 (BRD7) was identified as a nuclear transcriptional regulatory factor. BRD7 functions as a tumor suppressor in multiple cancers, including nasopharyngeal carcinoma (NPC). In this study, we reported a novel mechanism of BRD7 in NPC progression. We demonstrated that the expression of miR-141 was remarkably increased in NPC tissues and was negatively correlated with the expression of BRD7 and the survival rate of NPC patients. Decreased expression levels of miR-141, including the primary, the precursor and the mature forms of miR-141, were found in BRD7-overexpressing HEK293, 5-8F and HNE1 cells compared the control cells, while there was no obvious effect on the expression levels of the two critical enzymes Drosha and Dicer. BRD7 can negatively regulate the promoter activity of miR-141, while no obvious binding site of BRD7 was found in the potential promoter region of miR-141. Moreover, ectopic expression of miR-141 can significantly promote cell proliferation and inhibit apoptosis in NPC, and rescuing the expression of miR-141 in BRD7-overexpressing NPC cells could partially reverse the tumor suppressive effect of BRD7 on cell proliferation and tumor growth in vitro and in vivo. Furthermore, the activation of the PTEN/AKT pathway mediated by the overexpression of BRD7 could be inhibited by rescuing the expression of miR-141, which accordingly results in the partial restoration of cell proliferation and tumor growth. Our findings demonstrate that the BRD7/miR-141/PTEN/AKT axis has critical roles in the progression of NPC and provide some promising targets for the diagnosis and treatment of NPC.
authors.affiliation: Hunan Cancer Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, PR China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Hunan Cancer Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, PR China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: R
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Hunan Cancer Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, PR China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Niu
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tan
authors.affiliation: Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.affiliation: Hunan Cancer Hospital and The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, PR China.|Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: M
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000328:Adult; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D051057:Proto-Oncogene Proteins c-akt; D012334:RNA, Neoplasm; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C533895:MIRN141 microRNA, human; C494929:PTEN protein, human