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Expression of tumor suppressive microRNA-34a is associated with a reduced risk of bladder cancer recurrence
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Details:
  • Pubmed ID:
    25556547
  • Pubmed Central ID:
    PMC4485975
  • Description:
    Bladder cancer is the fourth most common cancer among men in the United States and more than half of patients experience recurrences within 5 years after initial diagnosis. Additional clinically informative and actionable biomarkers of the recurrent bladder cancer phenotypes are needed to improve screening and molecular therapeutic approaches for recurrence prevention. MicroRNA-34a (miR-34a) is a short noncoding regulatory RNA with tumor suppressive attributes. We leveraged our unique, large, population-based prognostic study of bladder cancer in New Hampshire, United States to evaluate miR-34a expression levels in individual tumor cells to assess prognostic value. We collected detailed exposure and medical history data, as well as tumor tissue specimens from bladder patients and followed them long-term for recurrence, progression and survival. Fluorescence-based in situ hybridization assays were performed on urothelial carcinoma tissue specimens (nā€‰=ā€‰229). A larger proportion of the nonmuscle invasive tumors had high levels of miR-34a within the carcinoma cells compared to those tumors that were muscle invasive. Patients with high miR-34a levels in their baseline nonmuscle invasive tumors experienced lower risks of recurrence (adjusted hazard ratio 0.57, 95% confidence interval 0.34-0.93). Consistent with these observations, we demonstrated a functional tumor suppressive role for miR-34a in cultured urothelial cells, including reduced matrigel invasion and growth in soft agar. Our results highlight the need for further clinical studies of miR-34a as a guide for recurrence screening and as a possible candidate therapeutic target in the bladder.

  • Document Type:
  • Collection(s):
  • Funding:
    5P42ES05947/ES/NIEHS NIH HHS/United States
    CA078609/CA/NCI NIH HHS/United States
    CA099500/CA/NCI NIH HHS/United States
    CA102327/CA/NCI NIH HHS/United States
    CA121382/CA/NCI NIH HHS/United States
    CA141017/CA/NCI NIH HHS/United States
    CA182659/CA/NCI NIH HHS/United States
    CA82354/CA/NCI NIH HHS/United States
    ES00002/ES/NIEHS NIH HHS/United States
    ES07373/ES/NIEHS NIH HHS/United States
    GM103506/GM/NIGMS NIH HHS/United States
    GM103534/GM/NIGMS NIH HHS/United States
    K07 CA102327/CA/NCI NIH HHS/United States
    K07CA102327/CA/NCI NIH HHS/United States
    LM009012/LM/NLM NIH HHS/United States
    P20 GM103534/GM/NIGMS NIH HHS/United States
    P20 RR018787/RR/NCRR NIH HHS/United States
    P20 RR024475/RR/NCRR NIH HHS/United States
    P30 CA023108/CA/NCI NIH HHS/United States
    P30 ES000002/ES/NIEHS NIH HHS/United States
    P42 ES005947/ES/NIEHS NIH HHS/United States
    P42 ES007373/ES/NIEHS NIH HHS/United States
    R01 CA078609/CA/NCI NIH HHS/United States
    R01 CA082354/CA/NCI NIH HHS/United States
    R01 LM009012/LM/NLM NIH HHS/United States
    R03 CA099500/CA/NCI NIH HHS/United States
    R03 CA121382/CA/NCI NIH HHS/United States
    R21 CA141017/CA/NCI NIH HHS/United States
    R21 CA182659/CA/NCI NIH HHS/United States
    RR018787/RR/NCRR NIH HHS/United States
    RR024475/RR/NCRR NIH HHS/United States
    RR028309/RR/NCRR NIH HHS/United States
    U58/DP000798/DP/NCCDPHP CDC HHS/United States
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