Abstract
TINCR is a well-known lncRNA which acts as a master regulator in somatic differentiation development. However, it is still unclear whether TINCR is also involved in caner occurrence and progression. In this study, we observed that TINCR was up-regulated in bladder cancer tissues and cells and contributed to oncogenesis and cancer progression. Silencing TINCR expression inhibited cell proliferation and promoted apoptosis in vitro, indicating that TINCR may be the potential therapeutic target for treating bladder urothelial carcinoma. Thus we used the synthetic biology approach to create theophylline controllable RNAi-based genetic switches which silenced TINCR in a dosage-dependent manner. Both RNAi-OFF and ON switches can be used to quantitatively control the expression of TINCR in bladder cancer to suppress the progression of bladder cancer. These findings suggest that lncRNA-TINCR could promote bladder cancer development and progression and artificial control of its expression through inducible RNAi may represent a new kind of therapeutic strategy for treating human bladder cancer.
Highlights
More attractive therapeutic approaches are definitely required
We demonstrate that Terminal differentiation-induced ncRNA (TINCR) is up-regulated in BCa tissues and cell lines (SW780 and 5637) and contributes to oncogenesis and cancer progression
The relative expression level of TINCR was measured by real-time qPCR in pair-matched specimens obtained from patients with BCa and 2 BCa cell lines
Summary
More attractive therapeutic approaches are definitely required. As mentioned above, the specific lncRNAs may provide novel therapeutic targets for the treatment of cancers. Benefited from synthetic biology, these natural switches can be engineered to respond to any signal of choice and to regulate any gene of interest in the related expression platforms[19]. The theophylline-dependent miRNA or shRNA regulators which function as the “RNAi-OFF switches” were highlighted in former studies[24,25,26]. Based on the engineering principles of medical synthetic biology, here, we presented the novel RNA regulators (theo-RNAi switches) which activate or inactivate the RNAi pathway to control TINCR expression in a theophylline dosage-dependent manner. We demonstrate that TINCR is up-regulated in BCa tissues and cell lines (SW780 and 5637) and contributes to oncogenesis and cancer progression.
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