High-throughput transcriptomic and RNAi analysis identifies AIM1, ERGIC1, TMED3 and TPX2 as potential drug targets in prostate cancer

Paula Vainio, J.-P. Mpindi, Pekka Kohonen, Vidal Fey, T. Mirtti, K.A. Alanen, Merja Perälä, Olli Kallioniemi, Kristiina Iljin (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

Prostate cancer is a heterogeneous group of diseases and there is a need for more efficient and targeted methods of treatment. In this study, the potential of gene expression data and RNA interference technique were combined to advance future personalized prostate cancer therapeutics. To distinguish the most promising in vivo prevalidated prostate cancer drug targets, a bioinformatic analysis was carried out using genome-wide gene expression data from 9873 human tissue samples. In total, 295 genes were selected for further functional studies in cultured prostate cancer cells due to their high mRNA expression in prostate, prostate cancer or in metastatic prostate cancer samples. Second, RNAi based cell viability assay was performed in VCaP and LNCaP prostate cancer cells. Based on the siRNA results, gene expression patterns in human tissues and novelty, endoplasmic reticulum function associated targets AIM1, ERGIC1 and TMED3, as well as mitosis regulating TPX2 were selected for further validation. AIM1, ERGIC1, and TPX2 were shown to be highly expressed especially in prostate cancer tissues, and high mRNA expression of ERGIC1 and TMED3 associated with AR and ERG oncogene expression. ERGIC1 silencing specifically regulated the proliferation of ERG oncogene positive prostate cancer cells and inhibited ERG mRNA expression in these cells, indicating that it is a potent drug target in ERG positive subgroup of prostate cancers. TPX2 expression associated with PSA failure and TPX2 silencing reduced PSA expression, indicating that TPX2 regulates androgen receptor mediated signaling. In conclusion, the combinatorial usage of microarray and RNAi techniques yielded in a large number of potential novel biomarkers and therapeutic targets, for future development of targeted and personalized approaches for prostate cancer management.
Original languageEnglish
Article numbere39801
JournalPLoS ONE
Volume7
Issue number6
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

Fingerprint

prostatic neoplasms
RNA Interference
transcriptomics
Prostatic Neoplasms
Cells
Throughput
Gene expression
drugs
Tissue
Pharmaceutical Preparations
Messenger RNA
Genes
Androgen Receptors
Biomarkers
Bioinformatics
Microarrays
Small Interfering RNA
Assays
oncogenes
Oncogenes

Cite this

Vainio, Paula ; Mpindi, J.-P. ; Kohonen, Pekka ; Fey, Vidal ; Mirtti, T. ; Alanen, K.A. ; Perälä, Merja ; Kallioniemi, Olli ; Iljin, Kristiina. / High-throughput transcriptomic and RNAi analysis identifies AIM1, ERGIC1, TMED3 and TPX2 as potential drug targets in prostate cancer. In: PLoS ONE. 2012 ; Vol. 7, No. 6.
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title = "High-throughput transcriptomic and RNAi analysis identifies AIM1, ERGIC1, TMED3 and TPX2 as potential drug targets in prostate cancer",
abstract = "Prostate cancer is a heterogeneous group of diseases and there is a need for more efficient and targeted methods of treatment. In this study, the potential of gene expression data and RNA interference technique were combined to advance future personalized prostate cancer therapeutics. To distinguish the most promising in vivo prevalidated prostate cancer drug targets, a bioinformatic analysis was carried out using genome-wide gene expression data from 9873 human tissue samples. In total, 295 genes were selected for further functional studies in cultured prostate cancer cells due to their high mRNA expression in prostate, prostate cancer or in metastatic prostate cancer samples. Second, RNAi based cell viability assay was performed in VCaP and LNCaP prostate cancer cells. Based on the siRNA results, gene expression patterns in human tissues and novelty, endoplasmic reticulum function associated targets AIM1, ERGIC1 and TMED3, as well as mitosis regulating TPX2 were selected for further validation. AIM1, ERGIC1, and TPX2 were shown to be highly expressed especially in prostate cancer tissues, and high mRNA expression of ERGIC1 and TMED3 associated with AR and ERG oncogene expression. ERGIC1 silencing specifically regulated the proliferation of ERG oncogene positive prostate cancer cells and inhibited ERG mRNA expression in these cells, indicating that it is a potent drug target in ERG positive subgroup of prostate cancers. TPX2 expression associated with PSA failure and TPX2 silencing reduced PSA expression, indicating that TPX2 regulates androgen receptor mediated signaling. In conclusion, the combinatorial usage of microarray and RNAi techniques yielded in a large number of potential novel biomarkers and therapeutic targets, for future development of targeted and personalized approaches for prostate cancer management.",
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High-throughput transcriptomic and RNAi analysis identifies AIM1, ERGIC1, TMED3 and TPX2 as potential drug targets in prostate cancer. / Vainio, Paula; Mpindi, J.-P.; Kohonen, Pekka; Fey, Vidal; Mirtti, T.; Alanen, K.A.; Perälä, Merja; Kallioniemi, Olli; Iljin, Kristiina (Corresponding Author).

In: PLoS ONE, Vol. 7, No. 6, e39801, 2012.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - High-throughput transcriptomic and RNAi analysis identifies AIM1, ERGIC1, TMED3 and TPX2 as potential drug targets in prostate cancer

AU - Vainio, Paula

AU - Mpindi, J.-P.

AU - Kohonen, Pekka

AU - Fey, Vidal

AU - Mirtti, T.

AU - Alanen, K.A.

AU - Perälä, Merja

AU - Kallioniemi, Olli

AU - Iljin, Kristiina

PY - 2012

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N2 - Prostate cancer is a heterogeneous group of diseases and there is a need for more efficient and targeted methods of treatment. In this study, the potential of gene expression data and RNA interference technique were combined to advance future personalized prostate cancer therapeutics. To distinguish the most promising in vivo prevalidated prostate cancer drug targets, a bioinformatic analysis was carried out using genome-wide gene expression data from 9873 human tissue samples. In total, 295 genes were selected for further functional studies in cultured prostate cancer cells due to their high mRNA expression in prostate, prostate cancer or in metastatic prostate cancer samples. Second, RNAi based cell viability assay was performed in VCaP and LNCaP prostate cancer cells. Based on the siRNA results, gene expression patterns in human tissues and novelty, endoplasmic reticulum function associated targets AIM1, ERGIC1 and TMED3, as well as mitosis regulating TPX2 were selected for further validation. AIM1, ERGIC1, and TPX2 were shown to be highly expressed especially in prostate cancer tissues, and high mRNA expression of ERGIC1 and TMED3 associated with AR and ERG oncogene expression. ERGIC1 silencing specifically regulated the proliferation of ERG oncogene positive prostate cancer cells and inhibited ERG mRNA expression in these cells, indicating that it is a potent drug target in ERG positive subgroup of prostate cancers. TPX2 expression associated with PSA failure and TPX2 silencing reduced PSA expression, indicating that TPX2 regulates androgen receptor mediated signaling. In conclusion, the combinatorial usage of microarray and RNAi techniques yielded in a large number of potential novel biomarkers and therapeutic targets, for future development of targeted and personalized approaches for prostate cancer management.

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JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

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