ABSTRACT
High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PHF8 with a specific chemical inhibitor, iPHF8, is potent in regulating YY1 methylation, ETC gene transcription, mROS production, and cell growth in colon and lung cancer cells. iPHF8 exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting the PHF8/YY1 axis has great potential to treat cancers.
Subject(s)
Lung Neoplasms , Transcription Factors , Humans , Transcription Factors/metabolism , Reactive Oxygen Species/metabolism , Histone Demethylases/metabolism , Histones/metabolism , Cell Transformation, Neoplastic , Lung Neoplasms/genetics , YY1 Transcription Factor/genetics , YY1 Transcription Factor/metabolismABSTRACT
A pot-based experiment was conducted to study the Cd tolerance and accumulation characteristics of four invasive herbs (Galinsoga quadriradiata, Panicum dichotomiflorum, Setaria geniculata, and Lolium persicum) under exposures of 0 (T0), 5 (T5), 25 (T25), and 50 mg·kg-1 (T50) soil Cd concentrations to screen for potential Cd accumulators for phytoremediation. The results showed that the biomasses of both shoots and roots of G. quadriradiata had no significant changes compared to the control (T0) samples under all Cd treatments, whereas the biomass of the other three Poaceae species significantly decreased under the T25 or T50 treatment. The results indicate that G. quadriradiata had stronger Cd tolerance than the other three species. The Cd concentrations in the shoots and roots of the four herbs significantly increased with an increase in soil Cd concentrations, but the shoot bioconcentration factors (SBCF) of the four plant species significantly decreased under T5, T25, and T50 treatment. The SBCF of G. quadriradiata and P. dichotomiflorum were greater than 1 whereas those of S. geniculata and L. persicum were lower than 1. The translocation factors (TF) of G. quadriradiata were 0.93, 0.73, and 1.04 under T5, T25, and T50 treatment, respectively, which were significantly higher than those of the other three plants under the same soil Cd concentration. In addition, both the total Cd and shoot Cd contents of G. quadriradiata were notably higher than in the other three species under the same Cd treatment. Moreover, 90% of the Cd in G. quadriradiata could be transferred aboveground, which was significantly higher than for the other three plants. Based on our comprehensive comparison of Cd tolerance and accumulation capacity, we suggest that G. quadriradiata is a high-Cd accumulator with considerable phytoremediation potential.
Subject(s)
Cadmium , Soil Pollutants , Biodegradation, Environmental , Cadmium/analysis , Plant Roots/chemistry , Soil , Soil Pollutants/analysisABSTRACT
A nitrogen management experiment with three nitrogen levels (0, 120, and 180 kg·hm-2, namely N0, N120, N180) and three nitrogen allocation modes (NA: base fertilizer 100%; NB: base fertilizer 70% + seedling fertilizer 30%; NC: base fertilizer 60% + jointing fertilizer 40%) was conducted at four sites (Chongqing, Renshou, Guanghan and Xichang) during two consecutive years, the SPAD value, canopy photosynthetic rate (CAP), photosynthetically active radia-tion (PAR) interception efficiency and grain yield were determined, and the nitrogen use efficiency and PAR use efficiency were calculated. The results showed that the SPAD of upper-most three leaves, CAP, PAR interception efficiency and grain yield were promoted with increasing nitrogen fertilizer, but nitrogen fertilizer use efficiency, productivity efficiency, uptake efficiency and use efficiency were decreased. The promoting effects of nitrogen fertilizer postponing were different among nitrogen levels, with the highest SPAD in N180 treatment and the highest CAP in N120 treatment. The light use efficiency of different nitrogen fertilization patterns differed among four sites. Furthermore, nitrogenous fertilizer postponing significantly increased nitrogen agricultural fertilizer use efficiency, productivity efficiency, uptake efficiency and apparent nitrogen recovery efficiency, but declined nitrogen use efficiency, and the performance of NC was better than NB. Among different sites, Guanghan had the highest SPAD, CAP, PAR interception efficiency and grain yield, Xichang had higher SPAD and nitrogen use efficiency, lower CAP and PAR use efficiency, Chongqing and Renshou had the lowest SPAD, light use efficiency, nitrogen use efficiency and grain yield. Biomass had significant positive relationships with grain yield, CPA, SPAD, and PAR interception efficiency. Therefore, the increase of nitrogen fertilizer could promote yield at all sites, and nitrogenous fertilizer postponing could further optimize grain yield component and improve nitrogen and light use effi-ciency. But the effects depended on the years and sites, thus a target nitrogen management mode should be site-specifically made.