The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex

John R. Prensner; Matthew K. Iyer; Anirban Sahu; Irfan A. Asangani; Qi Cao; Lalit Patel; Ismael A. Vergara; Elai Davicioni; Nicholas Erho; Mercedeh Ghadessi; Robert B. Jenkins; Timothy J. Triche; Rohit Malik; Rachel Bedenis; Natalie McGregor; Teng Ma; Wei Chen; Sumin Han; Xiaojun Jing; Xuhong Cao; Xiaoju Wang; Benjamin Chandler; Wei Yan; Javed Siddiqui; Lakshmi P. Kunju; Saravana M. Dhanasekaran; Kenneth J. Pienta; Felix Y. Feng; Arul M. Chinnaiyan

doi:10.1038/ng.2771

The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex

John R. Prensner, Matthew K. Iyer, Anirban Sahu, Irfan A. Asangani, Qi Cao, Lalit Patel, Ismael A. Vergara, Elai Davicioni, Nicholas Erho, Mercedeh Ghadessi, Robert B. Jenkins, Timothy J. Triche, Rohit Malik, Rachel Bedenis, Natalie McGregor, Teng Ma, Wei Chen, Sumin Han, Xiaojun Jing, Xuhong CaoXiaoju Wang, Benjamin Chandler, Wei Yan, Javed Siddiqui, Lakshmi P. Kunju, Saravana M. Dhanasekaran, Kenneth J. Pienta, Felix Y. Feng, Arul M. Chinnaiyan

Houston Methodist

Research output: Contribution to journal › Letter › peer-review

603 Scopus citations

Abstract

Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority. The molecular basis for this clinical heterogeneity remains incompletely understood. Here we characterize a long noncoding RNA termed SChLAP1 (second chromosome locus associated with prostate-1; also called LINC00913) that is overexpressed in a subset of prostate cancers. SChLAP1 levels independently predict poor outcomes, including metastasis and prostate cancer-specific mortality. In vitro and in vivo gain-of-function and loss-of-function experiments indicate that SChLAP1 is critical for cancer cell invasiveness and metastasis. Mechanistically, SChLAP1 antagonizes the genome-wide localization and regulatory functions of the SWI/SNF chromatin-modifying complex. These results suggest that SChLAP1 contributes to the development of lethal cancer at least in part by antagonizing the tumor-suppressive functions of the SWI/SNF complex.

Original language	English (US)
Pages (from-to)	1392-1403
Number of pages	12
Journal	Nature Genetics
Volume	45
Issue number	11
DOIs	https://doi.org/10.1038/ng.2771
State	Published - Nov 2013

ASJC Scopus subject areas

Genetics

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Prensner, J. R., Iyer, M. K., Sahu, A., Asangani, I. A., Cao, Q., Patel, L., Vergara, I. A., Davicioni, E., Erho, N., Ghadessi, M., Jenkins, R. B., Triche, T. J., Malik, R., Bedenis, R., McGregor, N., Ma, T., Chen, W., Han, S., Jing, X., ... Chinnaiyan, A. M. (2013). The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nature Genetics, 45(11), 1392-1403. https://doi.org/10.1038/ng.2771

Prensner, JR, Iyer, MK, Sahu, A, Asangani, IA, Cao, Q, Patel, L, Vergara, IA, Davicioni, E, Erho, N, Ghadessi, M, Jenkins, RB, Triche, TJ, Malik, R, Bedenis, R, McGregor, N, Ma, T, Chen, W, Han, S, Jing, X, Cao, X, Wang, X, Chandler, B, Yan, W, Siddiqui, J, Kunju, LP, Dhanasekaran, SM, Pienta, KJ, Feng, FY & Chinnaiyan, AM 2013, 'The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex', Nature Genetics, vol. 45, no. 11, pp. 1392-1403. https://doi.org/10.1038/ng.2771

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title = "The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex",

abstract = "Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority. The molecular basis for this clinical heterogeneity remains incompletely understood. Here we characterize a long noncoding RNA termed SChLAP1 (second chromosome locus associated with prostate-1; also called LINC00913) that is overexpressed in a subset of prostate cancers. SChLAP1 levels independently predict poor outcomes, including metastasis and prostate cancer-specific mortality. In vitro and in vivo gain-of-function and loss-of-function experiments indicate that SChLAP1 is critical for cancer cell invasiveness and metastasis. Mechanistically, SChLAP1 antagonizes the genome-wide localization and regulatory functions of the SWI/SNF chromatin-modifying complex. These results suggest that SChLAP1 contributes to the development of lethal cancer at least in part by antagonizing the tumor-suppressive functions of the SWI/SNF complex.",

author = "Prensner, \{John R.\} and Iyer, \{Matthew K.\} and Anirban Sahu and Asangani, \{Irfan A.\} and Qi Cao and Lalit Patel and Vergara, \{Ismael A.\} and Elai Davicioni and Nicholas Erho and Mercedeh Ghadessi and Jenkins, \{Robert B.\} and Triche, \{Timothy J.\} and Rohit Malik and Rachel Bedenis and Natalie McGregor and Teng Ma and Wei Chen and Sumin Han and Xiaojun Jing and Xuhong Cao and Xiaoju Wang and Benjamin Chandler and Wei Yan and Javed Siddiqui and Kunju, \{Lakshmi P.\} and Dhanasekaran, \{Saravana M.\} and Pienta, \{Kenneth J.\} and Feng, \{Felix Y.\} and Chinnaiyan, \{Arul M.\}",

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AU - Prensner, John R.

AU - Iyer, Matthew K.

AU - Sahu, Anirban

AU - Asangani, Irfan A.

AU - Cao, Qi

AU - Patel, Lalit

AU - Vergara, Ismael A.

AU - Davicioni, Elai

AU - Erho, Nicholas

AU - Ghadessi, Mercedeh

AU - Jenkins, Robert B.

AU - Triche, Timothy J.

AU - Malik, Rohit

AU - Bedenis, Rachel

AU - McGregor, Natalie

AU - Ma, Teng

AU - Chen, Wei

AU - Han, Sumin

AU - Jing, Xiaojun

AU - Cao, Xuhong

AU - Wang, Xiaoju

AU - Chandler, Benjamin

AU - Yan, Wei

AU - Siddiqui, Javed

AU - Kunju, Lakshmi P.

AU - Dhanasekaran, Saravana M.

AU - Pienta, Kenneth J.

AU - Feng, Felix Y.

AU - Chinnaiyan, Arul M.

PY - 2013/11

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N2 - Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority. The molecular basis for this clinical heterogeneity remains incompletely understood. Here we characterize a long noncoding RNA termed SChLAP1 (second chromosome locus associated with prostate-1; also called LINC00913) that is overexpressed in a subset of prostate cancers. SChLAP1 levels independently predict poor outcomes, including metastasis and prostate cancer-specific mortality. In vitro and in vivo gain-of-function and loss-of-function experiments indicate that SChLAP1 is critical for cancer cell invasiveness and metastasis. Mechanistically, SChLAP1 antagonizes the genome-wide localization and regulatory functions of the SWI/SNF chromatin-modifying complex. These results suggest that SChLAP1 contributes to the development of lethal cancer at least in part by antagonizing the tumor-suppressive functions of the SWI/SNF complex.

AB - Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority. The molecular basis for this clinical heterogeneity remains incompletely understood. Here we characterize a long noncoding RNA termed SChLAP1 (second chromosome locus associated with prostate-1; also called LINC00913) that is overexpressed in a subset of prostate cancers. SChLAP1 levels independently predict poor outcomes, including metastasis and prostate cancer-specific mortality. In vitro and in vivo gain-of-function and loss-of-function experiments indicate that SChLAP1 is critical for cancer cell invasiveness and metastasis. Mechanistically, SChLAP1 antagonizes the genome-wide localization and regulatory functions of the SWI/SNF chromatin-modifying complex. These results suggest that SChLAP1 contributes to the development of lethal cancer at least in part by antagonizing the tumor-suppressive functions of the SWI/SNF complex.

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The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex

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