H3K27 acetylation activated-PDLIM7 promotes castration-resistant prostate cancer progression by inducing O-Glycosylation of YAP1 protein.

Castration-resistant prostate cancer (CRPC) is a fatal disease that evolves from prostate cancer due to drug resistance after long-term androgen deprivation therapy. In this study, we aimed to find novel molecular targets for treating CRPC. Through peptidome, we screened out polypeptides dysregulated in the serum of CRPC patients. According to RT-qPCR analysis and cell viability detection, we chose PDZ and LIM Domain 7 (PDLIM7) as the research object. As demonstrated by loss-of-function assays, silencing of PDLIM7 could suppress CRPC cell proliferation, migration, and angiogenesis. Moreover, PDLIM7 knockdown enhanced the sensitivity of CRPC cells to docetaxel treatment. Subsequently, we found that CBP/p300 increases the H3K27ac level in the PDLIM7 promoter to activate PDLIM7. Mechanism experiments such as IP and western blot revealed that PDLIM7 interacted with YAP1 to induce O-Glycosylation of YAP1 and thus stabilize YAP1 protein. Rescue assays demonstrated that PDLIM7 promoted the malignant processes of CRPC cells through YAP1. Finally, an animal study validated that PDLIM7 aggravated tumor growth. In conclusion, our findings highlighted the oncogenic role of PDLIM7 upregulated by CBP/p300-induced H3K27ac enhancement in CRPC by stabilizing YAP1.

LNP-miR-155 cy5 Inhibitor Regulates the Copper Transporter via the ß-Catenin/TCF4/SLC31A1 Signal for Colorectal Cancer Therapy.

Lipid nanoparticle (LNP) delivery systems are widely used in the delivery of small-molecule drugs and nucleic acids. In this study, we prepared LNP-miR-155 by lipid nanomaterial technology and investigated the effects of LNP-miR-155 on ß-catenin/transcription factor 4 (TCF4)/solute carrier family 31 member 1/copper transporter 1 (SLC31A1/CTR1) signaling and copper transport in colorectal cancer. For this, we used an LNP-miR-155 cy5 inhibitor and LNP-miR-155 cy5 mimics for the transfection of HT-29/SW480 cells. The transfection efficiency and uptake efficiency were detected by immunofluorescence. Relevant cell assays confirmed that the LNP-miR-155 cy5 inhibitor mediates the regulation of copper transport through the ß-catenin/TCF4/SLC31A1 axis. The LNP-miR-155 cy5 inhibitor reduced cell proliferation, migration, and colony formation and promoted cell apoptosis. We also confirmed that miR-155 downregulates HMG box-containing protein 1 (HBP1) and adenomatous polyposis coli (APC) in cells and activates the function of ß-catenin/TCF4 signaling. In addition, we found that the copper transporter, SLC31A1, is highly expressed in colorectal cancer cells. Furthermore, we also found that the complex ß-catenin/TCF4 promotes the transcription of SLC31A1 by binding to its promoter region, which sustains the transport of copper from the extracellular region to the intracellular region and increases the activities of Cu2+-ATPase and superoxide dismutase (SOD). In summary, the LNP-miR-155 cy5 inhibitor regulates ß-catenin/TCF4 by downregulating SLC31A1-mediated copper transport and intracellular copper homeostasis.

HuR confers IL-17a-induced migration and invasion of gastric cancer cells via upregulation of Snail translation.

Human gastric cancer is a leading cause of cancer mortality in the world wide. We found that the expression of IL-17a was significantly increased in gastric cancer cells. Treatment with recombinant IL-17a (rIL-17a) can increase migration, invasion and epithelial to mesenchymal transition (EMT) of gastric cancer cells. Further, Snail, a key factor to regulate EMT, was significantly increased in rIL-17a-treated gastric cancer cells. While knockdown of Snail can abolish IL-17a-induced EMT of gastric cancer cells. Mechanistically, IL-17a can promote the translation efficiency of Snail, while had no effect on its mRNA expression or protein stability. Further, we found that IL-17a can increase the expression of HuR, which markedly promoted translation of Snail mRNA. While knockdown of HuR can reverse rIL-17a-induced expression of Snail and EMT of gastric cancer cells. Collectively, our data suggested that HuR confers IL-17a induced migration and invasion of gastric cancer cells via upregulation of Snail translation.

ZNF3 regulates proliferation, migration and invasion through MMP1 and TWIST in colorectal cancer.

Colorectal cancer (CRC) is a malignant tumor with a high incidence and mortality worldwide. Currently, the underlying molecular mechanisms of CRC are still unclear. Zinc finger protein 3 (ZNF3) is a zinc-finger transcription factor that has been reported as a candidate for breast cancer prognosis, suggesting its involvement in the regulation of tumorigenesis. However, the association between ZNF3 and CRC remains unknown. To investigate the role of ZNF3 in CRC, we first analyze the correlation between ZNF3 expression and CRC, and the results demonstrate that ZNF3 is highly expressed in CRC tissue and cells, which is associated with the age of CRC patients. In vitro studies show that ZNF3 overexpression promotes CRC cell migration. Compared to control cells, knockdown of ZNF3 markedly suppresses CRC cell proliferation, migration and invasion and promotes G0/G1 phase cell cycle arrest. The expressions of the EMT-related markers TWIST and MMP1 are significantly decreased when ZNF3 is silenced. Additionally, overexpression of MMP1 and TWIST exacerbates CRC cell proliferation, accelerates the S phase cell cycle in ZNF3-knockdown SW480 cells, and increases cell migration and invasion through Transwell chambers. These data suggest that ZNF3 is involved in cellular proliferation, migration and invasion by regulating MMP1 and TWIST in CRC cells.

Energy Reflection and Transmission at 2D Holographic Interfaces.

Scattering from conformal interfaces in two dimensions is universal in that the flux of reflected and transmitted energy does not depend on the details of the initial state. In this Letter, we present the first gravitational calculation of energy reflection and transmission coefficients for interfaces with thin-brane holographic duals. Our result for the reflection coefficient depends monotonically on the tension of the dual string anchored at the interface and obeys the lower bound recently derived from the averaged-null-energy condition in conformal field theory. The boundary-conformal-field-theory limit is recovered for infinite ratio of the central charges.