title: PVT1-derived miR-1207-5p promotes breast cancer cell growth by targeting STAT6.
abstract: Accumulating evidence indicates that ectopic expression of non-coding RNAs are responsible for breast cancer progression. Increased non-coding RNA PVT1, the host gene of microRNA-1207-5p (miR-1207-5p), has been associated with breast cancer proliferation. However, how PVT1 functions in breast cancer is still not clear. In this study, we show a PVT1-derived microRNA, miR-1207-5p, that promotes the proliferation of breast cancer cells by directly regulating STAT6. We first confirm the positive correlated expression pattern between PVT1 and miR-1207-5p by observing consistent induced expression by estrogen, and overexpression in breast cancer cell lines and breast cancer patient specimens. Moreover, silence of PVT1 also decreased miR-1207-5p expression. Furthermore, increased miR-1207-5p expression promoted, while decreased miR-1207-5p expression suppressed, cell proliferation, colony formation, and cell cycle progression in breast cancer cell lines. Mechanistically, a novel target of miR-1207-5p, STAT6, was identified by a luciferase reporter assay. Overexpression of miR-1207-5p decreased the levels of STAT6, which activated CDKN1A and CDKN1B to regulate the cell cycle. We also confirmed the reverse correlation of miR-1207-5p and STAT6 expression levels in breast cancer samples. Therefore, our findings reveal that PVT1-derived miR-1207-5p promotes the proliferation of breast cancer cells by targeting STAT6, which in turn controls CDKN1A and CDKN1B expression. These findings suggest miR-1207-5p might be a potential target for breast cancer therapy.
authors.affiliation: School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Blood Transfusion Branch, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Kong
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Fu
authors.affiliation: Schools of Laboratory Medicine, Tianjin Medical University, Tianjin, China.
authors.forename: Yunde
authors.initials: Y
authors.lastname: Liu
authors.affiliation: General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Clinical Laboratory Diagnostics, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics*; D050800:STAT6 Transcription Factor / Q000235:genetics*
chemical_list: C575047:MIRN1207 microRNA, human; D035683:MicroRNAs; C521123:PVT1 long-non-coding RNA, human; D062085:RNA, Long Noncoding; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human
keywords: Breast cancer; PVT1; STAT6; cell proliferation; miR-1207-5p