title: Linc-RoR promotes c-Myc expression through hnRNP I and AUF1.
abstract: Linc-RoR was originally identified to be a regulator for induced pluripotent stem cells in humans and it has also been implicated in tumorigenesis. However, the underlying mechanism of Linc-RoR-mediated gene expression in cancer is poorly understood. The present study demonstrates that Linc-RoR plays an oncogenic role in part through regulation of c-Myc expression. Linc-RoR knockout (KO) suppresses cell proliferation and tumor growth. In particular, Linc-RoR KO causes a significant decrease in c-Myc whereas re-expression of Linc-RoR in the KO cells restores the level of c-Myc. Mechanistically, Linc-RoR interacts with heterogeneous nuclear ribonucleoprotein (hnRNP) I and AU-rich element RNA-binding protein 1 (AUF1), respectively, with an opposite consequence to their interaction with c-Myc mRNA. While Linc-RoR is required for hnRNP I to bind to c-Myc mRNA, interaction of Linc-RoR with AUF1 inhibits AUF1 to bind to c-Myc mRNA. As a result, Linc-RoR may contribute to the increased stability of c-Myc mRNA. Although hnRNP I and AUF1 can interact with many RNA species and regulate their functions, with involvement of Linc-RoR they would be able to selectively regulate mRNA stability of specific genes such as c-Myc. Together, these results support a role for Linc-RoR in c-Myc expression in part by specifically enhancing its mRNA stability, leading to cell proliferation and tumorigenesis.
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Huang
authors.affiliation: Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA Department of Pharmacology/Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Tsui-Ting
authors.initials: TT
authors.lastname: Ho
authors.affiliation: Department of Respiration, Tongji Hospital affiliated to Tongji University, Shanghai, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Nanjiang
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Ding
authors.affiliation: Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China ymo@umc.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA Department of Pharmacology/Toxicology, University of Mississippi Medical Center, Jackson, MS, USA ymo@umc.edu.
authors.forename: Yin-Yuan
authors.initials: YY
authors.lastname: Mo
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C000630987:Hnrpd protein, mouse; C000588825:Linc-RNA-RoR, human; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D012333:RNA, Messenger