A basal-enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model

Xiying Fan; Glen A. Bjerke; Kent Riemondy; Li Wang; Rui Yi

doi:10.1002/mc.23112

A basal-enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model

Xiying Fan^*, Glen A. Bjerke, Kent Riemondy, Li Wang, Rui Yi

^*Corresponding author for this work

Pathology

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

1 Scopus citations

Abstract

MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer-enriched miRNA is required for prostate tumorigenesis. We identify miR-205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR-205 is not required for normal prostate development and homeostasis, genetic deletion of miR-205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR-205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR-205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR-205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR-205 in the progression of Pten null-induced prostate cancer.

Original language	English (US)
Pages (from-to)	2241-2253
Number of pages	13
Journal	Molecular Carcinogenesis
Volume	58
Issue number	12
DOIs	https://doi.org/10.1002/mc.23112
State	Published - Dec 1 2019

Funding

We thank D. Wang and all other members of the Yi laboratory for discussion and P. Muhlrad for reading the manuscript. We thank E. Olson (UT Southwest) for providing miR-21fl/fl mice and A. Palmer (CU Boulder) for providing human prostate cancer cell lines. We thank Y. Han for FACS sorting, K. Diener and B. Gao for Illumina sequencing. G.A.B. was supported by an American Cancer Society Postdoctoral Fellowship (129540-PF-16-059-01-RMC). This study was supported by NIH grant R01AR066703 and American Cancer Society Research Scholar Grant 124718-RSG-13-197-01-DDC to RY. We thank D. Wang and all other members of the Yi laboratory for discussion and P. Muhlrad for reading the manuscript. We thank E. Olson (UT Southwest) for providing miR‐21 mice and A. Palmer (CU Boulder) for providing human prostate cancer cell lines. We thank Y. Han for FACS sorting, K. Diener and B. Gao for Illumina sequencing. G.A.B. was supported by an American Cancer Society Postdoctoral Fellowship (129540‐PF‐16‐059‐01‐RMC). This study was supported by NIH grant R01AR066703 and American Cancer Society Research Scholar Grant 124718‐RSG‐13‐197‐01‐DDC to RY. fl/fl

Keywords

PI(3)K pathway
miRNAs
prostate cancer

ASJC Scopus subject areas

Molecular Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/mc.23112

Cite this

@article{06a994575e094eeba61cf16930004d19,

title = "A basal-enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model",

abstract = "MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer-enriched miRNA is required for prostate tumorigenesis. We identify miR-205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR-205 is not required for normal prostate development and homeostasis, genetic deletion of miR-205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR-205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR-205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR-205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR-205 in the progression of Pten null-induced prostate cancer.",

keywords = "PI(3)K pathway, miRNAs, prostate cancer",

author = "Xiying Fan and Bjerke, {Glen A.} and Kent Riemondy and Li Wang and Rui Yi",

note = "Funding Information: We thank D. Wang and all other members of the Yi laboratory for discussion and P. Muhlrad for reading the manuscript. We thank E. Olson (UT Southwest) for providing miR-21fl/fl mice and A. Palmer (CU Boulder) for providing human prostate cancer cell lines. We thank Y. Han for FACS sorting, K. Diener and B. Gao for Illumina sequencing. G.A.B. was supported by an American Cancer Society Postdoctoral Fellowship (129540-PF-16-059-01-RMC). This study was supported by NIH grant R01AR066703 and American Cancer Society Research Scholar Grant 124718-RSG-13-197-01-DDC to RY. Funding Information: We thank D. Wang and all other members of the Yi laboratory for discussion and P. Muhlrad for reading the manuscript. We thank E. Olson (UT Southwest) for providing miR‐21 mice and A. Palmer (CU Boulder) for providing human prostate cancer cell lines. We thank Y. Han for FACS sorting, K. Diener and B. Gao for Illumina sequencing. G.A.B. was supported by an American Cancer Society Postdoctoral Fellowship (129540‐PF‐16‐059‐01‐RMC). This study was supported by NIH grant R01AR066703 and American Cancer Society Research Scholar Grant 124718‐RSG‐13‐197‐01‐DDC to RY. fl/fl Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",

year = "2019",

month = dec,

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doi = "10.1002/mc.23112",

language = "English (US)",

volume = "58",

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AU - Fan, Xiying

AU - Bjerke, Glen A.

AU - Riemondy, Kent

AU - Wang, Li

AU - Yi, Rui

N1 - Funding Information: We thank D. Wang and all other members of the Yi laboratory for discussion and P. Muhlrad for reading the manuscript. We thank E. Olson (UT Southwest) for providing miR-21fl/fl mice and A. Palmer (CU Boulder) for providing human prostate cancer cell lines. We thank Y. Han for FACS sorting, K. Diener and B. Gao for Illumina sequencing. G.A.B. was supported by an American Cancer Society Postdoctoral Fellowship (129540-PF-16-059-01-RMC). This study was supported by NIH grant R01AR066703 and American Cancer Society Research Scholar Grant 124718-RSG-13-197-01-DDC to RY. Funding Information: We thank D. Wang and all other members of the Yi laboratory for discussion and P. Muhlrad for reading the manuscript. We thank E. Olson (UT Southwest) for providing miR‐21 mice and A. Palmer (CU Boulder) for providing human prostate cancer cell lines. We thank Y. Han for FACS sorting, K. Diener and B. Gao for Illumina sequencing. G.A.B. was supported by an American Cancer Society Postdoctoral Fellowship (129540‐PF‐16‐059‐01‐RMC). This study was supported by NIH grant R01AR066703 and American Cancer Society Research Scholar Grant 124718‐RSG‐13‐197‐01‐DDC to RY. fl/fl Publisher Copyright: © 2019 Wiley Periodicals, Inc.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer-enriched miRNA is required for prostate tumorigenesis. We identify miR-205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR-205 is not required for normal prostate development and homeostasis, genetic deletion of miR-205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR-205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR-205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR-205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR-205 in the progression of Pten null-induced prostate cancer.

AB - MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer-enriched miRNA is required for prostate tumorigenesis. We identify miR-205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR-205 is not required for normal prostate development and homeostasis, genetic deletion of miR-205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR-205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR-205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR-205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR-205 in the progression of Pten null-induced prostate cancer.

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ER -

A basal-enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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