ABSTRACT
Clear cell renal cell carcinoma (ccRCC) is the major subtype of renal cell carcinoma (RCC) that is resistant to conventional radiation and chemotherapy. It is a challenge to explore effective therapeutic targets and drugs for this kind of cancer. Transcription factor Krüppel-like factor 5 (KLF5) exerts diverse functions in various tumor types. By analyzing cohorts of the Cancer Genome Atlas (TCGA) data sets, we find that KLF5 expression is suppressed in ccRCC patients and higher level of KLF5 expression is associated with better prognostic outcome. Our further investigations demonstrate that KLF5 genomic loci are hypermethylated at proximal exon 4 and suppression of DNA methyltransferase 1 (DNMT1) expression by ShRNAs or a methylation inhibitor 5-Aza-CdR can recover KLF5 expression. Meanwhile, there is a negative correlation between expressions of KLF5 and DNMT1 in ccRCC tissues. Ectopic KLF5 expression inhibits ccRCC cell proliferation and migration/invasion in vitro and decreases xenograft growth and metastasis in vivo. Moreover, 5-Aza-CdR, a chemotherapy drug as DNMTs' inhibitor that can induce KLF5 expression, suppresses ccRCC cell growth, while knockdown of KLF5 abolishes 5-Aza-CdR-induced growth inhibition. Collectively, our data demonstrate that KLF5 inhibits ccRCC growth as a tumor suppressor and highlight the potential of 5-Aza-CdR to release KLF5 expression as a therapeutic modality for the treatment of ccRCC.
Subject(s)
Carcinoma, Renal Cell/metabolism , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , DNA Methylation/genetics , Kidney Neoplasms/metabolism , Kruppel-Like Transcription Factors/metabolism , Animals , Blotting, Western , Carcinoma, Renal Cell/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Cell Proliferation/physiology , Cell Survival/genetics , Cell Survival/physiology , DNA (Cytosine-5-)-Methyltransferase 1/genetics , DNA Methylation/physiology , Female , Gene Expression Regulation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic/physiology , HEK293 Cells , Humans , Immunohistochemistry , In Vitro Techniques , Kidney Neoplasms/genetics , Kruppel-Like Transcription Factors/genetics , Mice , Mice, Inbred BALB C , Mice, Nude , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
This paper introduces the methods improving the performance and stability of copper-phthalocyanine(CuPc) / fullerene (C60) small molecule solar cells by using tris-(8-hydroxyquinoline) aluminum(Alq3): cesium fluoride(CsF) composite cathode buffer layer. The device with Alq3:CsF composite cathode buffer layer with a 4 wt. % CsF at a thickness of 5 nm exhibits a power conversion efficiency (PCE) of up to 0.76%, which is an improvement of 49%, compared to a device with single Alq3 cathode buffer layer and half-lifetime of the cell in air at ambient circumstance without any encapsulation is almost 9.8 hours, 6 times higher than that of without buffer layer, so the stability is maintained. The main reason of the device performance improvement is that doping of CsF can adjust the interface energy alignment, optimize the electronic transmission characteristics of Alq3 and improve the short circuit current and the fill factor of the device using ultraviolet-visible absorption, external quantum efficiency and single-electron devices. Placed composite cathode buffer layer devices with different time in the air, by comparing and analyzing current voltage curve, Alq3:CsF can maintain a good stability as Alq3. Alq3:CsF layer can block the diffusion of oxygen and moisture so completely as to improve the lifetime of the device.
