Metabolic reprogramming is a hallmark of cancer. However, the roles of long noncoding RNAs (lncRNAs) in cancer metabolism, especially glucose metabolism remain largely unknown.In this study, we identified and functionally characterized a novel metabolism-related lncRNA, LINC00930, which was upregulated and associated with tumorigenesis, lymphatic invasion, metastasis, and poor prognosis in nasopharyngeal carcinoma (NPC). Functionally, LINC00930 was required for increased glycolysis activity and cell proliferation in multiple NPC models in vitro and in vivo. Mechanistically, LINC00930 served as a scaffold to recruit the RBBP5 and GCN5 complex to the PFKFB3 promoter and increased H3K4 trimethylation and H3K9 acetylation levels in the PFKFB3 promoter region, which epigenetically transactivating PFKFB3, and thus promoting glycolytic flux and cell cycle progression. Clinically, targeting LINC00930 and PFKFB3 in combination with radiotherapy induced tumor regression.Collectively, LINC00930 is mechanistically, functionally and clinically oncogenic in NPC. Targeting LINC00930 and its pathway may be meaningful for treating patients with NPC. 

https://jeccr.biomedcentral.com/track/pdf/10.1186/s13046-022-02282-9

Long noncoding RNA LINC00930 promotes PFKFB3-mediated tumor glycolysis and cell proliferation in nasopharyngeal carcinoma

The post-translational modifications (PTMs) of histone proteins play essential functions in shaping the chromatin environment. Alone or in combination, these PTMs create templates recognized by dedicated proteins or change the chemistry of chromatin, enabling a myriad of nuclear processes to occur. Referred to as cross-talk, the positive or negative impact of a PTM on another post-translational modification has rapidly emerged as a mechanism controlling nuclear transactions. One of those includes the stimulatory functions of histone H2B ubiquitylation on the methylation of histone H3 on K79 and K4 by Dot1L and COMPASS, respectively. While these findings were established early on, the structural determinants underlying the positive impact of H2B ubiquitylation on H3K79 and H3K4 methylation were resolved only recently. We will review the molecular features controlling these cross-talks and the impact of H3K27 tri-methylation on EZH2, when embedded in the PRC complex, activity.

/pdf/structural-paradigms-in-the-recognition-of-the-nucleosome-y7nrbgxpom.pdf

Structural Paradigms in the Recognition of the Nucleosome Core Particle by Histone Lysine Methyltransferases.

https://doi.org/10.1016/j.isci.2022.105736

Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins

Isl1 promotes gene transcription through physical interaction with Set1/Mll complexes

Dendritic cells(DCs) play a protective role in the antitumor immunity of most cancers, which can be divided into conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). Most current studies are only based on either cDCs or pDCs for the study of the relationship between DCs and breast cancer prognosis, without combining the two together. We aimed to select new biomarkers from pDCs and cDCs. In this paper, the xCell algorithm was first used to calculate the cellular abundance of 64 types of immune cells and stromal cells in tumor samples from the TCGA database, and the high-abundance pDC group and cDC group were divided according to the results of a survival analysis. Then, we looked for the co-expressed gene module of highly infiltrating pDC and cDC patients with a weighted correlation network analysis (WGCNA) and screened out the hub genes, including RBBP5, HNRNPU, PEX19, TPR, and BCL9. Finally, we analyzed the biological functions of the hub genes, and the results showed that RBBP5, TPR, and BCL9 were significantly related to the immune cells and prognosis of patients, and RBBP5 and BCL9 were involved in responding to TCF-related instructions of the Wnt pathway. In addition, we also evaluated the response of pDCs and cDCs with different abundances to chemotherapy, and the results showed that the higher the abundance of pDCs and cDCs, the higher their sensitivity to drugs. This paper revealed new biomarkers related to DCs—among them, BCL9, TPR, and RBBP5 were proven to be closely related to dendritic cells in cancer. For the first time, this paper puts forward that HNRNPU and PEX19 are related to the prognosis of dendritic cells in cancer, which also provides new possibilities for finding new targets for breast cancer immunotherapy.

/pdf/new-biomarkers-based-on-dendritic-cells-for-breast-cancer-1m5wiifp.pdf

New Biomarkers Based on Dendritic Cells for Breast Cancer Treatment and Prognosis Diagnosis

The Mixed Lineage Leukemia protein 1 (MLL1) plays an essential role in the maintenance of the histone H3 lysine 4 (H3K4) methylation status for gene expression during differentiation and development. The methyltransferase activity of MLL1 is regulated by three conserved core subunits, WDR5, RBBP5 and ASH2L. Here, we determined the structure of human RBBP5 and demonstrated its role in the assembly and regulation of the MLL1 complex. We identified an internal interaction between the WD40 propeller and the C-terminal distal region in RBBP5, which assisted the maintenance of the compact conformation of the MLL1 complex. We also discovered a vertebrate-specific motif in the C-terminal distal region of RBBP5 that contributed to nucleosome recognition and methylation of nucleosomes by the MLL1 complex. Our results provide new insights into functional conservation and evolutionary plasticity of the scaffold protein RBBP5 in the regulation of KMT2-family methyltransferase complexes.

/pdf/the-internal-interaction-in-rbbp5-regulates-assembly-and-3nwxhlkpjk.pdf

The internal interaction in RBBP5 regulates assembly and activity of MLL1 methyltransferase complex.

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The internal interaction in RBBP5 regulates assembly and activity of MLL1 methyltransferase complex.