Integrative genomic, transcriptomic, and RNAi analysis indicates a potential oncogenic role for FAM110B in castration-resistant prostate cancer

Paula Vainio, Maija Wolf, Henrik Edgren, Tao He, Pekka Kohonen, John Mpindi, F. Smit, G. Verhaegh, J. Schalken, Merja Perälä, Kristiina Iljin, Olli Kallioniemi (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

BACKGROUND: Castration‐resistant prostate cancer (CRPC) represents a therapeutic challenge for current medications.

METHOD: In order to explore the molecular mechanisms involved in CRPC progression and to identify new therapeutic targets, we analyzed a unique sample set of 11 CRPCs and 7 advanced tumors by array‐CGH and gene expression microarrays. The genome‐wide DNA and RNA data were integrated to identify genes whose overexpression was driven by their amplification. To assess the functional role of these genes, their expression was analyzed in a transcriptional data set of 329 clinical prostate cancers and the corresponding gene products were silenced using RNA interference in prostate cancer cells.

RESULTS: Six recurrent genetic targets were identified in the CRPCs; ATP1B1, AR, FAM110B, LAS1L, MYC, and YIPF6. In addition to AR and MYC, FAM110B emerged as a potential key gene involved in CRPC progression in a subset of the tumors. FAM110B was able to regulate AR signaling in prostate cancer cells and FAM110B itself was regulated by androgens. FAM110B siRNA inhibited the growth of prostate cancer cells in vitro, and this effect was substantially enhanced in androgen deficient conditions. Ectopic FAM110B expression in non‐cancerous epithelial prostate cells induced aneuploidy and impaired antigen presentation.

CONCLUSIONS: The DNA/RNA gene outlier detection combined with siRNA cell proliferation assay identified FAM110B as a potential growth promoting key gene for CRPC. FAM110B appears to have a key role in the androgen signaling and progression of CRPC impacting multiple cancer hallmarks and therefore highlighting a potential therapeutic target.
Original languageEnglish
Pages (from-to)789-802
Number of pages4
JournalThe Prostate
Volume72
Issue number7
DOIs
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

Fingerprint

Castration
RNA Interference
Prostatic Neoplasms
Androgens
Small Interfering RNA
Genes
RNA
Gene Expression
Neoplasms
Neoplasm Genes
DNA
Antigen Presentation
Aneuploidy
Growth
Prostate
Therapeutics
Epithelial Cells
Cell Proliferation

Keywords

  • aCGH
  • gene expression
  • gene silencing
  • prostate cancer cell growth
  • androgen receptor signaling

Cite this

Vainio, Paula ; Wolf, Maija ; Edgren, Henrik ; He, Tao ; Kohonen, Pekka ; Mpindi, John ; Smit, F. ; Verhaegh, G. ; Schalken, J. ; Perälä, Merja ; Iljin, Kristiina ; Kallioniemi, Olli. / Integrative genomic, transcriptomic, and RNAi analysis indicates a potential oncogenic role for FAM110B in castration-resistant prostate cancer. In: The Prostate. 2011 ; Vol. 72, No. 7. pp. 789-802.
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title = "Integrative genomic, transcriptomic, and RNAi analysis indicates a potential oncogenic role for FAM110B in castration-resistant prostate cancer",
abstract = "BACKGROUND: Castration‐resistant prostate cancer (CRPC) represents a therapeutic challenge for current medications.METHOD: In order to explore the molecular mechanisms involved in CRPC progression and to identify new therapeutic targets, we analyzed a unique sample set of 11 CRPCs and 7 advanced tumors by array‐CGH and gene expression microarrays. The genome‐wide DNA and RNA data were integrated to identify genes whose overexpression was driven by their amplification. To assess the functional role of these genes, their expression was analyzed in a transcriptional data set of 329 clinical prostate cancers and the corresponding gene products were silenced using RNA interference in prostate cancer cells.RESULTS: Six recurrent genetic targets were identified in the CRPCs; ATP1B1, AR, FAM110B, LAS1L, MYC, and YIPF6. In addition to AR and MYC, FAM110B emerged as a potential key gene involved in CRPC progression in a subset of the tumors. FAM110B was able to regulate AR signaling in prostate cancer cells and FAM110B itself was regulated by androgens. FAM110B siRNA inhibited the growth of prostate cancer cells in vitro, and this effect was substantially enhanced in androgen deficient conditions. Ectopic FAM110B expression in non‐cancerous epithelial prostate cells induced aneuploidy and impaired antigen presentation.CONCLUSIONS: The DNA/RNA gene outlier detection combined with siRNA cell proliferation assay identified FAM110B as a potential growth promoting key gene for CRPC. FAM110B appears to have a key role in the androgen signaling and progression of CRPC impacting multiple cancer hallmarks and therefore highlighting a potential therapeutic target.",
keywords = "aCGH, gene expression, gene silencing, prostate cancer cell growth, androgen receptor signaling",
author = "Paula Vainio and Maija Wolf and Henrik Edgren and Tao He and Pekka Kohonen and John Mpindi and F. Smit and G. Verhaegh and J. Schalken and Merja Per{\"a}l{\"a} and Kristiina Iljin and Olli Kallioniemi",
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doi = "10.1002/pros.21487",
language = "English",
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Vainio, P, Wolf, M, Edgren, H, He, T, Kohonen, P, Mpindi, J, Smit, F, Verhaegh, G, Schalken, J, Perälä, M, Iljin, K & Kallioniemi, O 2011, 'Integrative genomic, transcriptomic, and RNAi analysis indicates a potential oncogenic role for FAM110B in castration-resistant prostate cancer', The Prostate, vol. 72, no. 7, pp. 789-802. https://doi.org/10.1002/pros.21487

Integrative genomic, transcriptomic, and RNAi analysis indicates a potential oncogenic role for FAM110B in castration-resistant prostate cancer. / Vainio, Paula; Wolf, Maija; Edgren, Henrik; He, Tao; Kohonen, Pekka; Mpindi, John; Smit, F.; Verhaegh, G.; Schalken, J.; Perälä, Merja; Iljin, Kristiina; Kallioniemi, Olli (Corresponding Author).

In: The Prostate, Vol. 72, No. 7, 2011, p. 789-802.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Integrative genomic, transcriptomic, and RNAi analysis indicates a potential oncogenic role for FAM110B in castration-resistant prostate cancer

AU - Vainio, Paula

AU - Wolf, Maija

AU - Edgren, Henrik

AU - He, Tao

AU - Kohonen, Pekka

AU - Mpindi, John

AU - Smit, F.

AU - Verhaegh, G.

AU - Schalken, J.

AU - Perälä, Merja

AU - Iljin, Kristiina

AU - Kallioniemi, Olli

PY - 2011

Y1 - 2011

N2 - BACKGROUND: Castration‐resistant prostate cancer (CRPC) represents a therapeutic challenge for current medications.METHOD: In order to explore the molecular mechanisms involved in CRPC progression and to identify new therapeutic targets, we analyzed a unique sample set of 11 CRPCs and 7 advanced tumors by array‐CGH and gene expression microarrays. The genome‐wide DNA and RNA data were integrated to identify genes whose overexpression was driven by their amplification. To assess the functional role of these genes, their expression was analyzed in a transcriptional data set of 329 clinical prostate cancers and the corresponding gene products were silenced using RNA interference in prostate cancer cells.RESULTS: Six recurrent genetic targets were identified in the CRPCs; ATP1B1, AR, FAM110B, LAS1L, MYC, and YIPF6. In addition to AR and MYC, FAM110B emerged as a potential key gene involved in CRPC progression in a subset of the tumors. FAM110B was able to regulate AR signaling in prostate cancer cells and FAM110B itself was regulated by androgens. FAM110B siRNA inhibited the growth of prostate cancer cells in vitro, and this effect was substantially enhanced in androgen deficient conditions. Ectopic FAM110B expression in non‐cancerous epithelial prostate cells induced aneuploidy and impaired antigen presentation.CONCLUSIONS: The DNA/RNA gene outlier detection combined with siRNA cell proliferation assay identified FAM110B as a potential growth promoting key gene for CRPC. FAM110B appears to have a key role in the androgen signaling and progression of CRPC impacting multiple cancer hallmarks and therefore highlighting a potential therapeutic target.

AB - BACKGROUND: Castration‐resistant prostate cancer (CRPC) represents a therapeutic challenge for current medications.METHOD: In order to explore the molecular mechanisms involved in CRPC progression and to identify new therapeutic targets, we analyzed a unique sample set of 11 CRPCs and 7 advanced tumors by array‐CGH and gene expression microarrays. The genome‐wide DNA and RNA data were integrated to identify genes whose overexpression was driven by their amplification. To assess the functional role of these genes, their expression was analyzed in a transcriptional data set of 329 clinical prostate cancers and the corresponding gene products were silenced using RNA interference in prostate cancer cells.RESULTS: Six recurrent genetic targets were identified in the CRPCs; ATP1B1, AR, FAM110B, LAS1L, MYC, and YIPF6. In addition to AR and MYC, FAM110B emerged as a potential key gene involved in CRPC progression in a subset of the tumors. FAM110B was able to regulate AR signaling in prostate cancer cells and FAM110B itself was regulated by androgens. FAM110B siRNA inhibited the growth of prostate cancer cells in vitro, and this effect was substantially enhanced in androgen deficient conditions. Ectopic FAM110B expression in non‐cancerous epithelial prostate cells induced aneuploidy and impaired antigen presentation.CONCLUSIONS: The DNA/RNA gene outlier detection combined with siRNA cell proliferation assay identified FAM110B as a potential growth promoting key gene for CRPC. FAM110B appears to have a key role in the androgen signaling and progression of CRPC impacting multiple cancer hallmarks and therefore highlighting a potential therapeutic target.

KW - aCGH

KW - gene expression

KW - gene silencing

KW - prostate cancer cell growth

KW - androgen receptor signaling

U2 - 10.1002/pros.21487

DO - 10.1002/pros.21487

M3 - Article

VL - 72

SP - 789

EP - 802

JO - The Prostate

JF - The Prostate

SN - 0270-4137

IS - 7

ER -