Universität zu Köln

Gong, Xue, Siprashvili, Zurab, Eminaga, Okyaz, Shen, Zhewei ORCID: 0000-0002-5811-3521, Sato, Yusuke, Kume, Haruki, Homma, Yukio, Ogawa, Seishi, Khavari, Paul A., Pollack, Jonathan R. and Brooks, James D. (2017). Novel lincRNA SLINKY is a prognostic biomarker in kidney cancer. Oncotarget, 8 (12). S. 18657 - 18670. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Clear cell renal cell carcinomas (ccRCC) show a broad range of clinical behavior, and prognostic biomarkers are needed to stratify patients for appropriate management. We sought to determine whether long intergenic non-coding RNAs (lincRNAs) might predict patient survival. Candidate prognostic lincRNAs were identified by mining The Cancer Genome Atlas (TCGA) transcriptome (RNA-seq) data on 466 ccRCC cases (randomized into discovery and validation sets) annotated for similar to 21,000 lncRNAs. A previously uncharacterized lincRNA, SLINKY (Survival-predictive LINcRNA in KidneY cancer), was the top-ranked prognostic lincRNA, and validated in an independent University of Tokyo cohort (P=0.004). In multivariable analysis, SLINKY expression predicted overall survival independent of tumor stage and grade [TCGA HR=3.5 (CI, 2.2-5.7), P < 0.001; Tokyo HR=8.4 (CI, 1.8-40.2), P =0.007], and by decision tree, ROC and decision curve analysis, added independent prognostic value. In ccRCC cell lines, SLINKY knockdown reduced cancer cell proliferation (with cell-cycle G1 arrest) and induced transcriptome changes enriched for cell proliferation and survival processes. Notably, the genes affected by SLINKY knockdown in cell lines were themselves prognostic and correlated with SLINKY expression in the ccRCC patient samples. From a screen for binding partners, we identified direct binding of SLINKY to Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK), whose knockdown recapitulated SLINKY knockdown phenotypes. Thus, SLINKY is a robust prognostic biomarker in ccRCC, where it functions possibly together with HNRNPK in cancer cell proliferation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gong, Xue UNSPECIFIED UNSPECIFIED UNSPECIFIED Siprashvili, Zurab UNSPECIFIED UNSPECIFIED UNSPECIFIED Eminaga, Okyaz UNSPECIFIED UNSPECIFIED UNSPECIFIED Shen, Zhewei UNSPECIFIED orcid.org/0000-0002-5811-3521 UNSPECIFIED Sato, Yusuke UNSPECIFIED UNSPECIFIED UNSPECIFIED Kume, Haruki UNSPECIFIED UNSPECIFIED UNSPECIFIED Homma, Yukio UNSPECIFIED UNSPECIFIED UNSPECIFIED Ogawa, Seishi UNSPECIFIED UNSPECIFIED UNSPECIFIED Khavari, Paul A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pollack, Jonathan R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brooks, James D. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-236424
Journal or Publication Title:	Oncotarget
Volume:	8
Number:	12
Page Range:	S. 18657 - 18670
Date:	2017
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LONG NONCODING RNA; RENAL-CELL CARCINOMA; PREDICTS SURVIVAL; PROSTATE-CANCER; POOR-PROGNOSIS; EXPRESSION; GENE; IDENTIFICATION; ANNOTATION Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23642