A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability

J.B. Poell; R.J. van Haastert; T. de Gunst; I.J. Schultz; W.M. Gommans; M. Verheul; F. Cerisoli; P.I. van Noort; G.P. Prevost; R.Q. Schaapveld; E. Cuppen

doi:10.1371/journal.pone.0043569

A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability

J.B. Poell, R.J. van Haastert, T. de Gunst, I.J. Schultz, W.M. Gommans, M. Verheul, F. Cerisoli, P.I. van Noort, G.P. Prevost, R.Q. Schaapveld, E. Cuppen

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

55 Citations (Scopus)

Abstract

Malignant melanoma is an aggressive form of skin cancer with poor prognosis. Despite improvements in awareness and prevention of this disease, its incidence is rapidly increasing. MicroRNAs (miRNAs) are a class of small RNA molecules that regulate cellular processes by repressing messenger RNAs (mRNAs) with partially complementary target sites. Several miRNAs have already been shown to attenuate cancer phenotypes, by limiting proliferation, invasiveness, tumor angiogenesis, and stemness. Here, we employed a genome-scale lentiviral human miRNA expression library to systematically survey which miRNAs are able to decrease A375 melanoma cell viability. We highlight the strongest inhibitors of melanoma cell proliferation, including the miR-15/16, miR-141/200a and miR-96/182 families of miRNAs and miR-203. Ectopic expression of these miRNAs resulted in long-term inhibition of melanoma cell expansion, both in vitro and in vivo. We show specifically miR-16, miR-497, miR-96 and miR-182 are efficient effectors when introduced as synthetic miRNAs in several melanoma cell lines. Our study provides a comprehensive interrogation of miRNAs that interfere with melanoma cell proliferation and viability, and offers a selection of miRNAs that are especially promising candidates for application in melanoma therapy.

Original language	English
Pages (from-to)	43569
Journal	PLoS One
Volume	7
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0043569
Publication status	Published - 2012

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title = "A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability",

abstract = "Malignant melanoma is an aggressive form of skin cancer with poor prognosis. Despite improvements in awareness and prevention of this disease, its incidence is rapidly increasing. MicroRNAs (miRNAs) are a class of small RNA molecules that regulate cellular processes by repressing messenger RNAs (mRNAs) with partially complementary target sites. Several miRNAs have already been shown to attenuate cancer phenotypes, by limiting proliferation, invasiveness, tumor angiogenesis, and stemness. Here, we employed a genome-scale lentiviral human miRNA expression library to systematically survey which miRNAs are able to decrease A375 melanoma cell viability. We highlight the strongest inhibitors of melanoma cell proliferation, including the miR-15/16, miR-141/200a and miR-96/182 families of miRNAs and miR-203. Ectopic expression of these miRNAs resulted in long-term inhibition of melanoma cell expansion, both in vitro and in vivo. We show specifically miR-16, miR-497, miR-96 and miR-182 are efficient effectors when introduced as synthetic miRNAs in several melanoma cell lines. Our study provides a comprehensive interrogation of miRNAs that interfere with melanoma cell proliferation and viability, and offers a selection of miRNAs that are especially promising candidates for application in melanoma therapy.",

author = "J.B. Poell and {van Haastert}, R.J. and {de Gunst}, T. and I.J. Schultz and W.M. Gommans and M. Verheul and F. Cerisoli and {van Noort}, P.I. and G.P. Prevost and R.Q. Schaapveld and E. Cuppen",

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year = "2012",

doi = "10.1371/journal.pone.0043569",

language = "English",

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pages = "43569",

journal = "PLoS One",

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T1 - A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability

AU - Poell, J.B.

AU - van Haastert, R.J.

AU - de Gunst, T.

AU - Schultz, I.J.

AU - Gommans, W.M.

AU - Verheul, M.

AU - Cerisoli, F.

AU - van Noort, P.I.

AU - Prevost, G.P.

AU - Schaapveld, R.Q.

AU - Cuppen, E.

N1 - Reporting year: 2012

PY - 2012

Y1 - 2012

N2 - Malignant melanoma is an aggressive form of skin cancer with poor prognosis. Despite improvements in awareness and prevention of this disease, its incidence is rapidly increasing. MicroRNAs (miRNAs) are a class of small RNA molecules that regulate cellular processes by repressing messenger RNAs (mRNAs) with partially complementary target sites. Several miRNAs have already been shown to attenuate cancer phenotypes, by limiting proliferation, invasiveness, tumor angiogenesis, and stemness. Here, we employed a genome-scale lentiviral human miRNA expression library to systematically survey which miRNAs are able to decrease A375 melanoma cell viability. We highlight the strongest inhibitors of melanoma cell proliferation, including the miR-15/16, miR-141/200a and miR-96/182 families of miRNAs and miR-203. Ectopic expression of these miRNAs resulted in long-term inhibition of melanoma cell expansion, both in vitro and in vivo. We show specifically miR-16, miR-497, miR-96 and miR-182 are efficient effectors when introduced as synthetic miRNAs in several melanoma cell lines. Our study provides a comprehensive interrogation of miRNAs that interfere with melanoma cell proliferation and viability, and offers a selection of miRNAs that are especially promising candidates for application in melanoma therapy.

AB - Malignant melanoma is an aggressive form of skin cancer with poor prognosis. Despite improvements in awareness and prevention of this disease, its incidence is rapidly increasing. MicroRNAs (miRNAs) are a class of small RNA molecules that regulate cellular processes by repressing messenger RNAs (mRNAs) with partially complementary target sites. Several miRNAs have already been shown to attenuate cancer phenotypes, by limiting proliferation, invasiveness, tumor angiogenesis, and stemness. Here, we employed a genome-scale lentiviral human miRNA expression library to systematically survey which miRNAs are able to decrease A375 melanoma cell viability. We highlight the strongest inhibitors of melanoma cell proliferation, including the miR-15/16, miR-141/200a and miR-96/182 families of miRNAs and miR-203. Ectopic expression of these miRNAs resulted in long-term inhibition of melanoma cell expansion, both in vitro and in vivo. We show specifically miR-16, miR-497, miR-96 and miR-182 are efficient effectors when introduced as synthetic miRNAs in several melanoma cell lines. Our study provides a comprehensive interrogation of miRNAs that interfere with melanoma cell proliferation and viability, and offers a selection of miRNAs that are especially promising candidates for application in melanoma therapy.

U2 - 10.1371/journal.pone.0043569

DO - 10.1371/journal.pone.0043569

M3 - Article

SN - 1932-6203

VL - 7

SP - 43569

JO - PLoS One

JF - PLoS One

IS - 8

ER -

A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability

Abstract

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