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Deregulation of either RNA polymerase I (Pol I)-directed transcription or expression of signal transducer and activator of transcription 3 (STAT3) correlates closely with tumorigenesis. However, the connection between STAT3 and Pol I-directed transcription hasn't been investigated.The role of STAT3 in Pol I-directed transcription was determined using combined techniques. The regulation of tumor cell growth mediated by STAT3 and Pol I products was analyzed in vitro and in vivo. RNAseq, ChIP assays and rescue assays were used to uncover the mechanism of Pol I transcription mediated by STAT3.STAT3 expression positively correlates with Pol I product levels and cancer cell growth. The inhibition of STAT3 or Pol I products suppresses cell growth. Mechanistically, STAT3 activates Pol I-directed transcription by enhancing the recruitment of the Pol I transcription machinery to the rDNA promoter. STAT3 directly activates Rpa34 gene transcription by binding to the RPA34 promoter, which enhances the occupancies of the Pol II transcription machinery factors at this promoter. Cancer patients with RPA34 high expression lead to poor survival probability and short survival time.STAT3 potentiates Pol I-dependent transcription and tumor cell growth by activating RPA34 in vitro and in vivo.

RNA polymerase III (Pol III) products play essential roles in ribosome assembly, protein synthesis, and cell survival. Deregulation of Pol-III-directed transcription is closely associated with tumorigenesis. However, the regulatory pathways or factors controlling Pol-III-directed transcription remain to be investigated. In this study, we identified a novel role of EGR1 in Pol-III-directed transcription. We found that Filamin A (FLNA) silencing stimulated EGR1 expression at both RNA and protein levels. EGR1 expression positively correlated with Pol III product levels and cell proliferation activity. Mechanistically, EGR1 downregulation dampened the occupancies of Pol III transcription machinery factors at the loci of Pol III target genes. Alteration of EGR1 expression did not affect the expression of p53, c-MYC, and Pol III general transcription factors. Instead, EGR1 activated RhoA expression and inhibited PTEN expression in several transformed cell lines. We found that PTEN silencing, rather than RhoA overexpression, could reverse the inhibition of Pol-III-dependent transcription and cell proliferation caused by EGR1 downregulation. EGR1 could positively regulate AKT phosphorylation levels and is required for the inhibition of Pol-III-directed transcription mediated by FLNA. The findings from this study indicate that EGR1 can promote Pol-III-directed transcription and cell proliferation by controlling the PTEN/AKT signalling pathway.

RNA polymerase III (pol III) products play fundamental roles in a variety of cellular processes, including protein synthesis and cancer cell proliferation. In addition, dysregulation of pol III-directed transcription closely correlates with tumorigenesis. It is therefore of interest to identify novel pathways or factors governing pol III-directed transcription. Here, we show that transcription factor (TF) GATA binding protein 4 (GATA4) expression in SaOS2 cells was stimulated by the silencing of filamin A (FLNA), a repressor of pol III-directed transcription, suggesting that GATA4 is potentially associated with the regulation of pol III-directed transcription. Indeed, we show that GATA4 expression positively correlates with pol III-mediated transcription and tumor cell proliferation. Mechanistically, we found that GATA4 depletion inhibits the occupancies of the pol III transcription machinery factors at the loci of pol III target genes by reducing expression of both TFIIIB subunit TFIIB-related factor 1 and TFIIIC subunit general transcription factor 3C subunit 2 (GTF3C2). GATA4 has been shown to activate specificity factor 1 (Sp1) gene transcription by binding to the Sp1 gene promoter, and Sp1 has been confirmed to activate pol III gene transcription by directly binding to both Brf1 and Gtf3c2 gene promoters. Thus, the findings from this study suggest that GATA4 links FLNA and Sp1 signaling to form an FLNA/GATA4/Sp1 axis to modulate pol III-directed transcription and transformed cell proliferation. Taken together, these results provide novel insights into the regulatory mechanism of pol III-directed transcription.

The DC circuit breaker technology is one of the key technologies to build multi-terminal DC transmission network. Active DC vacuum circuit breaker (DCVCB) has become the research object. Based on the continuous transition model(CTM) and variable-step 4th-order Runge-Kutta method, sheath development stage during the post-arc dielectric recovery has been simulated and analyzed. Then the influence of major variables, including arc energy, contact erosion rate, and axial magnetic field between contacts, on sheath growth of post-arc dielectric recovery have been analyzed. The results show that the sheath thickness grows exponentially with time, and higher arc energy and contact erosion rate will result in larger initial ion density, longer ion decay time and slower sheath development. The stronger axial magnetic field will reduce initial ion density and promote sheath growth.