Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression

Yajia Zhang; Sethuramasundaram Pitchiaya; Marcin Cieślik; Yashar S Niknafs; Jean C-Y Tien; Yasuyuki Hosono; Matthew K Iyer; Sahr Yazdani; Shruthi Subramaniam; Sudhanshu K Shukla; Xia Jiang; Lisha Wang; Tzu-Ying Liu; Michael Uhl; Alexander R Gawronski; Yuanyuan Qiao; Lanbo Xiao; Saravana M Dhanasekaran; Kristin M Juckette; Lakshmi P Kunju; Xuhong Cao; Utsav Patel; Mona Batish; Girish C Shukla; Michelle T Paulsen; Mats Ljungman; Hui Jiang; Rohit Mehra; Rolf Backofen; Cenk S Sahinalp; Susan M Freier; Andrew T Watt; Shuling Guo; John T Wei; Felix Y Feng; Rohit Malik; Arul M Chinnaiyan

doi:10.1038/s41588-018-0120-1

Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression

Nat Genet. 2018 Jun;50(6):814-824. doi: 10.1038/s41588-018-0120-1. Epub 2018 May 28.

Authors

Yajia Zhang^{1

2

3

4}, Sethuramasundaram Pitchiaya^{1

2}, Marcin Cieślik^{1

2}, Yashar S Niknafs^{1

5}, Jean C-Y Tien^{1

2}, Yasuyuki Hosono¹, Matthew K Iyer^{1

4}, Sahr Yazdani¹, Shruthi Subramaniam¹, Sudhanshu K Shukla^{1

6}, Xia Jiang¹, Lisha Wang¹, Tzu-Ying Liu⁷, Michael Uhl⁸, Alexander R Gawronski⁹, Yuanyuan Qiao^{1

2

10}, Lanbo Xiao¹, Saravana M Dhanasekaran^{1

2}, Kristin M Juckette¹, Lakshmi P Kunju^{1

2

10}, Xuhong Cao^{1

11}, Utsav Patel¹², Mona Batish^{12

13}, Girish C Shukla¹⁴, Michelle T Paulsen^{10

15}, Mats Ljungman^{10

15}, Hui Jiang^{7

10}, Rohit Mehra^{2

10

16}, Rolf Backofen⁸, Cenk S Sahinalp^{17

18}, Susan M Freier¹⁹, Andrew T Watt¹⁹, Shuling Guo¹⁹, John T Wei¹⁶, Felix Y Feng^{1

10

15

20

21}, Rohit Malik^{1

22}, Arul M Chinnaiyan^{23

24

25

26

27

28

29}

Affiliations

¹ Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
² Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
³ Molecular and Cellular Pathology Program, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Computational Medicine and Bioinformatics, Ann Arbor, MI, USA.
⁵ Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA.
⁶ Department of Biosciences and Bioengineering, Indian Institute of Technology Dharwad, Dharwad, India.
⁷ Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
⁸ Department of Computer Science and Centre for Biological Signaling Studies (BIOSS), University of Freiburg, Freiburg, Germany.
⁹ School of Computing Science, Simon Fraser University, Burnaby, British Columbia, Canada.
¹⁰ Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
¹¹ Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA.
¹² New Jersey Medical School, Rutgers University, Newark, NJ, USA.
¹³ Department of Medical Laboratory Sciences, University of Delaware, Newark, DE, USA.
¹⁴ Department of Biological, Geological and Environmental Sciences, Center for Gene Regulation in Health and Disease, Cleveland State Univesity, Cleveland, OH, USA.
¹⁵ Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
¹⁶ Department of Urology, University of Michigan, Ann Arbor, MI, USA.
¹⁷ School of Informatics and Computing, Indiana University, Bloomington, IN, USA.
¹⁸ Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
¹⁹ Ionis Pharmaceuticals, Carlsbad, CA, USA.
²⁰ Breast Oncology Program, University of Michigan, Ann Arbor, MI, USA.
²¹ Departments of Radiation Oncology, Urology, and Medicine, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
²² Bristol-Myers Squibb, Princeton, NJ, USA.
²³ Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA. arul@umich.edu.
²⁴ Department of Pathology, University of Michigan, Ann Arbor, MI, USA. arul@umich.edu.
²⁵ Department of Computational Medicine and Bioinformatics, Ann Arbor, MI, USA. arul@umich.edu.
²⁶ Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA. arul@umich.edu.
²⁷ Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA. arul@umich.edu.
²⁸ Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA. arul@umich.edu.
²⁹ Department of Urology, University of Michigan, Ann Arbor, MI, USA. arul@umich.edu.

Abstract

The androgen receptor (AR) plays a critical role in the development of the normal prostate as well as prostate cancer. Using an integrative transcriptomic analysis of prostate cancer cell lines and tissues, we identified ARLNC1 (AR-regulated long noncoding RNA 1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA-RNA interaction. ARLNC1 knockdown suppressed AR expression, global AR signaling and prostate cancer growth in vitro and in vivo. Taken together, these data support a role for ARLNC1 in maintaining a positive feedback loop that potentiates AR signaling during prostate cancer progression and identify ARLNC1 as a novel therapeutic target.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Androgens / genetics
Androgens / metabolism
Cell Line, Tumor
Disease Progression
Gene Expression Regulation, Neoplastic
Humans
Male
Prostate / physiology
Prostatic Neoplasms / genetics*
Prostatic Neoplasms / metabolism
Prostatic Neoplasms / pathology
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
Receptors, Androgen / genetics*
Receptors, Androgen / metabolism
Signal Transduction

Substances

AR protein, human
Androgens
RNA, Long Noncoding
Receptors, Androgen

Abstract

Publication types

MeSH terms

Substances

Grants and funding