miR-148a dependent apoptosis of bladder cancer cells is mediated in part by the epigenetic modifier DNMT1

Alan P. Lombard, Benjamin A. Mooso, Stephen J. Libertini, Rebecca M. Lim, Rachel M. Nakagawa, Kathleen D. Vidallo, Nicole C. Costanzo, Paramita M Ghosh, Maria Mudryj

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Urothelial cell carcinoma of the bladder (UCCB) is the most common form of bladder cancer and it is estimated that ∼15,000 people in the United States succumbed to this disease in 2013. Bladder cancer treatment options are limited and research to understand the molecular mechanisms of this disease is needed to design novel therapeutic strategies. Recent studies have shown that microRNAs play pivotal roles in the progression of cancer. miR-148a has been shown to serve as a tumor suppressor in cancers of the prostate, colon, and liver, but its role in bladder cancer has never been elucidated. Here we show that miR-148a is down-regulated in UCCB cell lines. We demonstrate that overexpression of miR-148a leads to reduced cell viability through an increase in apoptosis rather than an inhibition of proliferation. We additionally show that miR-148a exerts this effect partially by attenuating expression of DNA methyltransferase 1 (DNMT1). Finally, our studies demonstrate that treating cells with both miR-148a and either cisplatin or doxorubicin is either additive or synergistic in causing apoptosis. These data taken together suggest that miR-148a is a tumor suppressor in UCCB and could potentially serve as a novel therapeutic for this malignancy.

Original languageEnglish (US)
JournalMolecular Carcinogenesis
DOIs
StateAccepted/In press - 2015

Fingerprint

Methyltransferases
Urinary Bladder Neoplasms
Epigenomics
Apoptosis
Urinary Bladder
DNA
Carcinoma
Neoplasms
Liver Neoplasms
MicroRNAs
Doxorubicin
Colonic Neoplasms
Cisplatin
Prostatic Neoplasms
Cell Survival
Cell Line
Therapeutics
Research

Keywords

  • Apoptosis
  • Bladder cancer
  • Cell cycle
  • Cisplatin
  • DNA methyltransferase (DNMT1)
  • Doxorubicin
  • MiR-148a

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

miR-148a dependent apoptosis of bladder cancer cells is mediated in part by the epigenetic modifier DNMT1. / Lombard, Alan P.; Mooso, Benjamin A.; Libertini, Stephen J.; Lim, Rebecca M.; Nakagawa, Rachel M.; Vidallo, Kathleen D.; Costanzo, Nicole C.; Ghosh, Paramita M; Mudryj, Maria.

In: Molecular Carcinogenesis, 2015.

Research output: Contribution to journalArticle

Lombard, Alan P. ; Mooso, Benjamin A. ; Libertini, Stephen J. ; Lim, Rebecca M. ; Nakagawa, Rachel M. ; Vidallo, Kathleen D. ; Costanzo, Nicole C. ; Ghosh, Paramita M ; Mudryj, Maria. / miR-148a dependent apoptosis of bladder cancer cells is mediated in part by the epigenetic modifier DNMT1. In: Molecular Carcinogenesis. 2015.
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abstract = "Urothelial cell carcinoma of the bladder (UCCB) is the most common form of bladder cancer and it is estimated that ∼15,000 people in the United States succumbed to this disease in 2013. Bladder cancer treatment options are limited and research to understand the molecular mechanisms of this disease is needed to design novel therapeutic strategies. Recent studies have shown that microRNAs play pivotal roles in the progression of cancer. miR-148a has been shown to serve as a tumor suppressor in cancers of the prostate, colon, and liver, but its role in bladder cancer has never been elucidated. Here we show that miR-148a is down-regulated in UCCB cell lines. We demonstrate that overexpression of miR-148a leads to reduced cell viability through an increase in apoptosis rather than an inhibition of proliferation. We additionally show that miR-148a exerts this effect partially by attenuating expression of DNA methyltransferase 1 (DNMT1). Finally, our studies demonstrate that treating cells with both miR-148a and either cisplatin or doxorubicin is either additive or synergistic in causing apoptosis. These data taken together suggest that miR-148a is a tumor suppressor in UCCB and could potentially serve as a novel therapeutic for this malignancy.",
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AU - Costanzo, Nicole C.

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