Identification of let-7f-5p as a novel biomarker of recurrence in non-muscle invasive bladder cancer.
Identification of let-7f-5p as a novel biomarker of recurrence in non-muscle invasive bladder cancer.
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DOI：
10.3233/cbm-191322
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发表时间：
2020-06
期刊：
影响因子：
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通讯作者：
K. Shee;J. Seigne;M. Karagas;C. Marsit;J. Hinds;A. Schned;J. Pettus;D. Armstrong;T. Miller;A. Andrew
中科院分区：
文献类型：
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作者：
K. Shee;J. Seigne;M. Karagas;C. Marsit;J. Hinds;A. Schned;J. Pettus;D. Armstrong;T. Miller;A. Andrew
BACKGROUND Among patients diagnosed with non-muscle invasive bladder cancer (NMIBC), 30% to 70% experience recurrences within 6 to 12 years of diagnosis. The need to screen for these events every 3 to 6 months and ultimately annually by cystoscopy makes bladder cancer one of the most expensive malignancies to manage. OBJECTIVE The of this study was to identify reproducible prognostic microRNAs in resected non-muscle invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype as potential biomarkers and molecular therapeutic targets. METHODS Two independent cohorts of NMIBC patients were analyzed using a biomarker discovery and validation approach, respectively. RESULTS miRNA Let-7f-5p showed the strongest association with recurrence across both cohorts. Let-7f-5p levels in urine and plasma were both found to be significantly correlated with levels in tumor tissue. We assessed the therapeutic potential of targeting Lin28, a negative regulator of Let-7f-5p, with small-molecule inhibitor C1632. Lin28 inhibition significantly increased levels of Let-7f-5p expression and led to significant inhibition of viability and migration of HTB-2 cells. CONCLUSIONS We have identified Let-7f-5p as a miRNA biomarker of recurrence in NMIBC tumors. We further demonstrate that targeting Lin28, a negative regulator of Let-7f-5p, represents a novel potential therapeutic opportunity in NMIBC.
