title: RNPC1 enhances progesterone receptor functions by regulating its mRNA stability in breast cancer.
abstract: Progesterone receptor (PR) could activate transcriptional process involved in normal mammary gland proliferation and breast cancer development. Moreover, PR expression is an important marker of luminal breast cancer, which is associated with good prognosis and indicates better responding to endocrine therapies. The regulation of PR expression was studied mainly on its post-translational levels. In this study, we found PR was positively regulated by RNA-binding region-containing protein 1 (RNPC1), a RNA-binding protein, in PR positive breast cancer. Overexpression of RNPC1 increased, whereas knockdown of RNPC1 decreased, the level of PR protein and transcripts. Additionally, we demonstrated that RNPC1 could bind to PR mRNA via AU-rich elements (AREs) within PR 3'-untranslated region (3'-UTR) and then enhance PR mRNA stability. Moreover, we proved that progesterone-dependent PR functions which could induce breast cancer proliferation were enhanced by RNPC1, both in vitro and in vivo. Conclusively, we revealed a novel mechanism by which PR could be regulated by RNPC1 via stabilizing its mRNA.
authors.affiliation: Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Lou
authors.affiliation: Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Chunlian
authors.initials: C
authors.lastname: Li
authors.affiliation: Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.affiliation: Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Tian-Song
authors.initials: TS
authors.lastname: Xia
authors.affiliation: Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Xujie
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research Division of Clinical Pharmacology, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Ji-Fu
authors.initials: JF
authors.lastname: Wei
authors.affiliation: Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D063307:AU Rich Elements / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D011485:Protein Binding; D034622:RNA Interference; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D020413:3' Untranslated Regions; D011372:Progestins; C515435:RBM38 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011980:Receptors, Progesterone; D011374:Progesterone
keywords: RNPC1; breast cancer; mRNA stability; progesterone receptor; proliferation