title: HSPC111 governs breast cancer growth by regulating ribosomal biogenesis.
abstract: Activation of c-Myc plays a decisive role in the development of many human cancers. As a transcription factor, c-Myc facilitates cell growth and proliferation by directly transcribing a multitude of targets, including rRNAs and ribosome proteins. However, how to elucidate the deregulation of rRNAs and ribosome proteins driven by c-Myc in cancer remains a significant challenge and thus warrants close investigation. In this report, a crucial role for the HSPC111 (NOP16) multiprotein complex in governing ribosomal biogenesis and tumor growth was determined. It was discovered that enhanced HSPC111 expression paralleled the upregulation of c-Myc and was directly regulated by c-Myc in breast cancer cells. Knockdown of HSPC111 dramatically reduced the occurrence of tumorigenesis in vivo, and largely restrained tumor cell growth in vitro and in vivo. In stark contrast, HSPC111 overexpression significantly promoted tumor cell growth. Biochemically, it was demonstrated that RNA 3'-phosphate cyclase (RTCD1/RTCA) interacted with HSPC111, and RTCD1 was involved in the HSPC111 multiprotein complex in regulating rRNA production and ribosomal biogenesis. Moreover, HSPC111 and RTCD1 synergistically modulated cell growth and cellular size through commanding rRNA synthesis and ribosome assembly coupled to protein production. Finally, overall survival analysis revealed that concomitant upregulation of HSPC111 and RTCD1 correlated with the worst prognosis in a breast cancer cohort.
  
  
  CONCLUSIONS
  Inhibition of HSPC111-dependent ribosomal biosynthesis and protein synthesis is a promising therapeutic strategy to diminish breast cancer tumor progression.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China or Professor Yong Xu, Department of Urology, Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China. sjliu@rcees.ac.cn.
authors.forename: Changwen
authors.initials: C
authors.lastname: Zhang
authors.forename: Chunyang
authors.initials: C
authors.lastname: Yin
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Qian
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Sijin
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D008025:Ligases / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism*; D014162:Transfection
chemical_list: C530131:NOP16 protein, human; D011506:Proteins; D012335:RNA, Ribosomal; D034741:RNA, Small Interfering; D008025:Ligases; C037451:RNA 3'-terminal phosphate cyclase