Genome-Wide CRISPR Screen Identifies Protein Pathways Modulating Tau Protein Levels in Neurons

Researchers reported a genome-wide CRISPR screen to identify modulators of endogenous tau protein for the first time. Primary screens performed in SH-SY5Y cells, identified positive and negative regulators of tau protein levels.
[Communications Biology]
Sanchez, C. G., Acker, C. M., Gray, A., Varadarajan, M., Song, C., Cochran, N. R., Paula, S., Lindeman, A., An, S., McAllister, G., Alford, J., Reece-Hoyes, J., Russ, C., Craig, L., Capre, K., Doherty, C., Hoffman, G. R., Luchansky, S. J., Polydoro, M., … Elwood, F. (2021). Genome-wide CRISPR screen identifies protein pathways modulating tau protein levels in neurons. Communications Biology, 4(1), 1–14. https://doi.org/10.1038/s42003-021-02272-1 Cite
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CircC16orf62 Promotes Hepatocellular Carcinoma Progression through the miR-138-5p/PTK2/AKT Axis

Gain or loss-of-function studies indicated that the reduction of CircC16orf62 expression promoted the proliferation, invasion, and glycolysis of hepatocellular carcinoma in vitro and in vivo.
[Cell Death & Disease]
Zhang, S., Lu, Y., Jiang, H.-Y., Cheng, Z.-M., Wei, Z.-J., Wei, Y.-H., Liu, T., Xia, B.-J., Zhao, X.-Y., Huang, Y., Zou, X., Liu, R., & Zhou, S. (2021). CircC16orf62 promotes hepatocellular carcinoma progression through the miR-138-5p/PTK2/AKT axis. Cell Death & Disease, 12(6), 1–13. https://doi.org/10.1038/s41419-021-03866-7 Cite
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AR-mTOR-SRF Axis Regulates HMMR Expression in Human Prostate Cancer Cells

The authors reported that mammalian target of rapamycin (mTOR) is a key regulator of hyaluronan-mediated motility receptor (HMMR) expression, for which its kinase activity is required. Pharmacological inhibitors of mTOR markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells.
[Biomolecules & Therapeutics]
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Oncogene-Induced Maladaptive Activation of Trained Immunity in the Pathogenesis and Treatment of Erdheim-Chester Disease

Researchers reveal oncogene-induced, maladaptive induction of trained immunity in the pathogenesis of a human inflammatory myeloid neoplasm, Erdheim-Chester disease, characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production.
[Blood]
Biavasco, R., Molteni, R., Stefanoni, D., Nemkov, T., Netea, M. G., Domínguez-Andrés, J., Arts, R. J., Merelli, I., Mazza, D., Zambrano, S., Panigada, M., Cantoni, E., Tengesdal, I., Maksud, P., Piras, F., De Luca, G., Cassina, L., Distefano, G., Loffreda, A., … Cavalli, G. (2021). Oncogene-induced maladaptive activation of trained immunity in the pathogenesis and treatment of Erdheim-Chester disease. Blood, blood.2020009594. https://doi.org/10.1182/blood.2020009594 Cite
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Reliance on Cox10 and Oxidative Metabolism for Antigen-Specific NK Cell Expansion

Mice with an inducible NK-specific deletion of Cox10, which encodes a component of electron transport chain complex IV, were generated to investigate the role of oxidative phosphorylation in NK cells during murine cytomegalovirus infection.
[Cell Reports]
Mah-Som, A. Y., Keppel, M. P., Tobin, J. M., Kolicheski, A., Saucier, N., Sexl, V., French, A. R., Wagner, J. A., Fehniger, T. A., & Cooper, M. A. (2021). Reliance on Cox10 and oxidative metabolism for antigen-specific NK cell expansion. Cell Reports, 35(9). https://doi.org/10.1016/j.celrep.2021.109209 Cite
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PPDPF Alleviates Hepatic Steatosis through Inhibition of mTOR Signaling

Scientists found that liver-specific knockout of pancreatic progenitor cell differentiation and proliferation factor (PPDPF) led to spontaneous fatty liver formation in a mouse model at 32 weeks of age on chow diets, which was enhanced by HFD.
[Nature Communications]
Ma, N., Wang, Y.-K., Xu, S., Ni, Q.-Z., Zheng, Q.-W., Zhu, B., Cao, H.-J., Jiang, H., Zhang, F.-K., Yuan, Y.-M., Zhang, E.-B., Chen, T.-W., Xia, J., Ding, X.-F., Chen, Z.-H., Zhang, X.-P., Wang, K., Cheng, S.-Q., Qiu, L., … Xie, D. (2021). PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling. Nature Communications, 12(1), 3059. https://doi.org/10.1038/s41467-021-23285-8 Cite
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Dynamic Regulation of B Cell Complement Signaling Is Integral to Germinal Center Responses

Scientists found that, as part of a physiologic program, germinal centers B cells repressed expression of decay-accelerating factor and other complement C3 convertase regulators via BCL6, but increased the expression of C5b-9 inhibitor CD59.
[Nature Immunology]
Cumpelik, A., Heja, D., Hu, Y., Varano, G., Ordikhani, F., Roberto, M. P., He, Z., Homann, D., Lira, S. A., Dominguez-Sola, D., & Heeger, P. S. (2021). Dynamic regulation of B cell complement signaling is integral to germinal center responses. Nature Immunology, 1–12. https://doi.org/10.1038/s41590-021-00926-0 Cite
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In Vivo Screen Identifies a SIK Inhibitor That Induces β Cell Proliferation through a Transient UPR

Single-cell transcriptomic analyses of mouse β cells demonstrate that HG-9-91-01 induces a wave of activating transcription factor (ATF)6-dependent unfolded protein response (UPR) before cell cycle entry.
[Nature Metabolism]
Charbord, J., Ren, L., Sharma, R. B., Johansson, A., Ågren, R., Chu, L., Tworus, D., Schulz, N., Charbord, P., Stewart, A. F., Wang, P., Alonso, L. C., & Andersson, O. (2021). In vivo screen identifies a SIK inhibitor that induces β cell proliferation through a transient UPR. Nature Metabolism, 3(5), 682–700. https://doi.org/10.1038/s42255-021-00391-x Cite
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Notch3 Inhibits Cell Proliferation and Tumorigenesis and Predicts Better Prognosis in Breast Cancer through Transactivating PTEN

Investigators studied the interaction between Notch receptors (Notch1-4) and PTEN, and demonstrated that Notch3 inhibited breast cancer proliferation and suppressed tumorigenesis by transactivating PTEN expression.
[Cell Death & Disease]
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Phytochemicals from Ajwa Dates Pulp Extract Induce Apoptosis in Human Triple-Negative Breast Cancer by Inhibiting AKT/mTOR Pathway and Modulating Bcl-2 Family Proteins

Researchers analyzed the phytoconstituents in ethanolic Ajwa Dates Pulp Extract by liquid chromatography-mass spectrometry and investigated anticancer effects against MDA-MB-231 cells.
[Scientific Reports]
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A Novel Dual HDAC and HSP90 Inhibitor, MPT0G449, Downregulates Oncogenic Pathways in Human Acute Leukemia In Vitro and In Vivo

Scientists suggested that the dual inhibition of HDAC and HSP90 could suppress the expression of oncogenic pathways in acute leukemia, and MPT0G449 represented a novel therapeutic for anticancer treatment.
[Oncogenesis]
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