LncRNA DGCR5 Isoform-1 Silencing Suppresses the Malignant Phenotype of Clear Cell Renal Cell Carcinoma via miR-211-5p/Snail Signal Axis.

Long non-coding RNAs (lncRNAs) play important roles during the initiation and progression of cancer. We identified DiGeorge Syndrome Critical Region Gene 5 (DGCR5) as a clear cell renal cell carcinoma (ccRCC) cancer- and lineage-specific lncRNA. Agarose gel electrophoresis analysis and sanger sequencing verified two main isoforms of DGCR5 in ccRCC patient tissues and cell lines. Quantitative polymerase chain reaction further demonstrated that the expression level of DGCR5 major isoform (isoform-1) was higher in ccRCC tissues than that in papillary/chromophobe RCC and other multiple solid malignant tumors. We investigate the biological functions of DGCR5 isoform-1 in ccRCC and show that DGCR5 isoform-1 exerts a tumor-promoting effect in ccRCC. DGCR5 isoform-1 is localized in cytoplasm and shares the same binding sequence to the tumor-suppressive miR-211-5p with the epithelial-to-mesenchymal transition key component SNAI. Furthermore, cellular and molecular experiments demonstrate that DGCR5 isoform-1 could sequester miR-211-5p, leading to the elevation of Snail protein and downregulation of its downstream targets and further promoting ccRCC cell proliferation and migration. Thus, our study indicates that DGCR5 isoform-1 could contribute to ccRCC progression by sponging miR-211-5p through regulating the expression of Snail protein and could serve as a reliable diagnostic biomarker in ccRCC.

Fault detection for discrete-time switched systems with sensor stuck faults and servo inputs.

This paper addresses the fault detection problem of switched systems with servo inputs and sensor stuck faults. The attention is focused on designing a switching law and its associated fault detection filters (FDFs). The proposed switching law uses only the current states of FDFs, which guarantees the residuals are sensitive to the servo inputs with known frequency ranges in faulty cases and robust against them in fault-free case. Thus, the arbitrarily small sensor stuck faults, including outage faults can be detected in finite-frequency domain. The levels of sensitivity and robustness are measured in terms of the finite-frequency H- index and l2-gain. Finally, the switching law and FDFs are obtained by the solution of a convex optimization problem.