miR-152 down-regulation is associated with MET up-regulation in leiomyosarcoma and undifferentiated pleomorphic sarcoma

Laura Pazzaglia, Chiara Novello, Amalia Conti, Serena Pollino, Piero Picci, Maria Serena Benassi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: Highly aggressive adult soft tissue sarcomas (STS), i.e., leiomyosarcomas (LMS) and undifferentiated pleomorphic sarcomas (UPS), present complex genomic anomalies and overall 5-year survival rates of 20 to 40%. Here, we aimed to identify new biomarkers that may be employed to improve the treatment of non-translocation STS patients. We validated 12 miRNAs implicated in tumor development using primary STS samples and selected miR-152 for further analysis in STS-derived cell lines. Methods: 59 primary STS samples (27 LMS and 32 UPS) and 10 matched normal control tissues were included in the study, as well as 3 STS-derived cell lines (HT1080, SW872 and SKLMS1) and a normal control mesenchymal cell line (hMSC). miRNA expression analyses were performed using a TaqMan microRNA Array platform and qRT-PCR (miR-152), respectively. The expression levels of the putative miR-152 targets MET and KIT were assessed using qRT-PCR and immunohistochemistry on tissue microarrays, respectively. In addition, various functional analyses were performed before and after miR-152 transfection into SKLMS1 cells. Results: We found that 12 pre-selected miRNAs were down-regulated in primary STS tumor samples compared to its normal control samples. A statistically significant miR-152 down-regulation was found to be accompanied by high MET and KIT mRNA levels in both the primary samples and the STS-derived cell lines tested. miR-152 transfection in SKLMS1 cells led to a reduction in KIT and MET mRNA and protein levels which, in turn, was associated with a transient down-regulation of the PI3K/AKT pathway, a transient decrease in cell growth, and a transient increase in both apoptotic and S-phase cells. Conclusions: Our data indicate that over-expression of MET and KIT in primary STS samples and its derived cell lines is associated with miR-152 down-regulation. This shift may play a role in STS development and, thus, may be used to identify patients at risk. The effect of MET down-regulation on downstream signaling pathways, such as the PI3K/AKT pathway, may provide a basis for the future design of novel STS treatment strategies.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalCellular Oncology
DOIs
Publication statusAccepted/In press - Nov 29 2016

Fingerprint

Leiomyosarcoma
Sarcoma
Up-Regulation
Down-Regulation
MicroRNAs
Cell Line
Phosphatidylinositol 3-Kinases
Transfection
Polymerase Chain Reaction
Messenger RNA
S Phase
Neoplasms
Survival Rate
Biomarkers

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

Cite this

miR-152 down-regulation is associated with MET up-regulation in leiomyosarcoma and undifferentiated pleomorphic sarcoma. / Pazzaglia, Laura; Novello, Chiara; Conti, Amalia; Pollino, Serena; Picci, Piero; Benassi, Maria Serena.

In: Cellular Oncology, 29.11.2016, p. 1-12.

Research output: Contribution to journalArticle

@article{09cd38a94ca2436daa8f86a32bccc4ab,
title = "miR-152 down-regulation is associated with MET up-regulation in leiomyosarcoma and undifferentiated pleomorphic sarcoma",
abstract = "Purpose: Highly aggressive adult soft tissue sarcomas (STS), i.e., leiomyosarcomas (LMS) and undifferentiated pleomorphic sarcomas (UPS), present complex genomic anomalies and overall 5-year survival rates of 20 to 40{\%}. Here, we aimed to identify new biomarkers that may be employed to improve the treatment of non-translocation STS patients. We validated 12 miRNAs implicated in tumor development using primary STS samples and selected miR-152 for further analysis in STS-derived cell lines. Methods: 59 primary STS samples (27 LMS and 32 UPS) and 10 matched normal control tissues were included in the study, as well as 3 STS-derived cell lines (HT1080, SW872 and SKLMS1) and a normal control mesenchymal cell line (hMSC). miRNA expression analyses were performed using a TaqMan microRNA Array platform and qRT-PCR (miR-152), respectively. The expression levels of the putative miR-152 targets MET and KIT were assessed using qRT-PCR and immunohistochemistry on tissue microarrays, respectively. In addition, various functional analyses were performed before and after miR-152 transfection into SKLMS1 cells. Results: We found that 12 pre-selected miRNAs were down-regulated in primary STS tumor samples compared to its normal control samples. A statistically significant miR-152 down-regulation was found to be accompanied by high MET and KIT mRNA levels in both the primary samples and the STS-derived cell lines tested. miR-152 transfection in SKLMS1 cells led to a reduction in KIT and MET mRNA and protein levels which, in turn, was associated with a transient down-regulation of the PI3K/AKT pathway, a transient decrease in cell growth, and a transient increase in both apoptotic and S-phase cells. Conclusions: Our data indicate that over-expression of MET and KIT in primary STS samples and its derived cell lines is associated with miR-152 down-regulation. This shift may play a role in STS development and, thus, may be used to identify patients at risk. The effect of MET down-regulation on downstream signaling pathways, such as the PI3K/AKT pathway, may provide a basis for the future design of novel STS treatment strategies.",
author = "Laura Pazzaglia and Chiara Novello and Amalia Conti and Serena Pollino and Piero Picci and Benassi, {Maria Serena}",
year = "2016",
month = "11",
day = "29",
doi = "10.1007/s13402-016-0306-4",
language = "English",
pages = "1--12",
journal = "Cellular oncology (Dordrecht)",
issn = "2211-3428",
publisher = "IOS Press",

}

TY - JOUR

T1 - miR-152 down-regulation is associated with MET up-regulation in leiomyosarcoma and undifferentiated pleomorphic sarcoma

AU - Pazzaglia, Laura

AU - Novello, Chiara

AU - Conti, Amalia

AU - Pollino, Serena

AU - Picci, Piero

AU - Benassi, Maria Serena

PY - 2016/11/29

Y1 - 2016/11/29

N2 - Purpose: Highly aggressive adult soft tissue sarcomas (STS), i.e., leiomyosarcomas (LMS) and undifferentiated pleomorphic sarcomas (UPS), present complex genomic anomalies and overall 5-year survival rates of 20 to 40%. Here, we aimed to identify new biomarkers that may be employed to improve the treatment of non-translocation STS patients. We validated 12 miRNAs implicated in tumor development using primary STS samples and selected miR-152 for further analysis in STS-derived cell lines. Methods: 59 primary STS samples (27 LMS and 32 UPS) and 10 matched normal control tissues were included in the study, as well as 3 STS-derived cell lines (HT1080, SW872 and SKLMS1) and a normal control mesenchymal cell line (hMSC). miRNA expression analyses were performed using a TaqMan microRNA Array platform and qRT-PCR (miR-152), respectively. The expression levels of the putative miR-152 targets MET and KIT were assessed using qRT-PCR and immunohistochemistry on tissue microarrays, respectively. In addition, various functional analyses were performed before and after miR-152 transfection into SKLMS1 cells. Results: We found that 12 pre-selected miRNAs were down-regulated in primary STS tumor samples compared to its normal control samples. A statistically significant miR-152 down-regulation was found to be accompanied by high MET and KIT mRNA levels in both the primary samples and the STS-derived cell lines tested. miR-152 transfection in SKLMS1 cells led to a reduction in KIT and MET mRNA and protein levels which, in turn, was associated with a transient down-regulation of the PI3K/AKT pathway, a transient decrease in cell growth, and a transient increase in both apoptotic and S-phase cells. Conclusions: Our data indicate that over-expression of MET and KIT in primary STS samples and its derived cell lines is associated with miR-152 down-regulation. This shift may play a role in STS development and, thus, may be used to identify patients at risk. The effect of MET down-regulation on downstream signaling pathways, such as the PI3K/AKT pathway, may provide a basis for the future design of novel STS treatment strategies.

AB - Purpose: Highly aggressive adult soft tissue sarcomas (STS), i.e., leiomyosarcomas (LMS) and undifferentiated pleomorphic sarcomas (UPS), present complex genomic anomalies and overall 5-year survival rates of 20 to 40%. Here, we aimed to identify new biomarkers that may be employed to improve the treatment of non-translocation STS patients. We validated 12 miRNAs implicated in tumor development using primary STS samples and selected miR-152 for further analysis in STS-derived cell lines. Methods: 59 primary STS samples (27 LMS and 32 UPS) and 10 matched normal control tissues were included in the study, as well as 3 STS-derived cell lines (HT1080, SW872 and SKLMS1) and a normal control mesenchymal cell line (hMSC). miRNA expression analyses were performed using a TaqMan microRNA Array platform and qRT-PCR (miR-152), respectively. The expression levels of the putative miR-152 targets MET and KIT were assessed using qRT-PCR and immunohistochemistry on tissue microarrays, respectively. In addition, various functional analyses were performed before and after miR-152 transfection into SKLMS1 cells. Results: We found that 12 pre-selected miRNAs were down-regulated in primary STS tumor samples compared to its normal control samples. A statistically significant miR-152 down-regulation was found to be accompanied by high MET and KIT mRNA levels in both the primary samples and the STS-derived cell lines tested. miR-152 transfection in SKLMS1 cells led to a reduction in KIT and MET mRNA and protein levels which, in turn, was associated with a transient down-regulation of the PI3K/AKT pathway, a transient decrease in cell growth, and a transient increase in both apoptotic and S-phase cells. Conclusions: Our data indicate that over-expression of MET and KIT in primary STS samples and its derived cell lines is associated with miR-152 down-regulation. This shift may play a role in STS development and, thus, may be used to identify patients at risk. The effect of MET down-regulation on downstream signaling pathways, such as the PI3K/AKT pathway, may provide a basis for the future design of novel STS treatment strategies.

UR - http://www.scopus.com/inward/record.url?scp=85000444285&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85000444285&partnerID=8YFLogxK

U2 - 10.1007/s13402-016-0306-4

DO - 10.1007/s13402-016-0306-4

M3 - Article

SP - 1

EP - 12

JO - Cellular oncology (Dordrecht)

JF - Cellular oncology (Dordrecht)

SN - 2211-3428

ER -