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  • Title: Long non-coding RNA UCA1 promotes cisplatin/gemcitabine resistance through CREB modulating miR-196a-5p in bladder cancer cells.
    Author: Pan J, Li X, Wu W, Xue M, Hou H, Zhai W, Chen W.
    Journal: Cancer Lett; 2016 Nov 01; 382(1):64-76. PubMed ID: 27591936.
    Abstract:
    Chemoresistance constitutes the major failing of clinical therapy for bladder cancer. However, the molecular mechanisms involved in the chemoresistance of bladder cancer are unclear. Long non-coding RNAs (lncRNAs) have been implicated in chemotherapeutic drug resistance. Urothelial Cancer Associated 1 (UCA1), an lncRNA, is reportedly upregulated in human bladder carcinoma and promotes cancer cell proliferation, migration, invasion, and drug resistance. In the present study, knockdown of UCA1 decreased chemosensitivity to cisplatin/gemcitabine by suppressing cell proliferation and inducing apoptosis, while overexpression of UCA1 increased chemosensitivity in bladder cancer cells. Moreover, UCA1 activated transcription factor CREB which led to miR-196a-5p expression by binding with its promoter. miR-196a-5p induction is involved in UCA1 inhibition of apoptosis induced by cisplatin/gemcitabine via targeting p27Kip1. These results provide a novel UCA1-CREB-miR-196a-5p paradigm to explain in part how UCA1 functions in cisplatin/gemcitabine resistance, and suggest that UCA1 may be a potential therapeutic target for chemotherapy in bladder cancer.
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