Biology subjects

Bu, Q.

Publications and source records attributed to Bu, Q..

5 recordsLinked to original sources

bioRxiv2025

BACH1 promotes hepatocellular carcinoma progression by targeting PDP1 towards the PI3K-AKT-mTOR signaling activation

Hepatocellular carcinoma (HCC) is remaining to be accepted as a major challenge against public health, because of its high incidence and mortality. Herein, we explored underlying molecular mechanisms by which BTB and CNC homology 1 (BACH1) facilitated progression of HCC. Functional experiments indicated that BACH1 promoted the proliferation, clonogenicity, cycle progression of HCC cells, and inhibited apoptosis. Knockout of BACH1 decreased mitochondrial membrane potential, augmented reactive oxygen species (ROS) generation, induced cell apoptosis, and reduced malignant growth of xenograft neoplasms in mice. Mechanistic experiments revealed that BACH1 bound to the ARE sites in the promoter region of pyruvate dehydrogenase phosphatase catalytic subunit 1 (PDP1), so to activate its transcriptional expression and promote cellular energy metabolism. Interestingly, BACH1 enables activation of the cell growth-related TGF-{beta}1/SMAD signaling pathway, which further promoted the malignant proliferation of HCC cells. Of note, PDP1 functions as a tumor promoter, since lowering its expression levels suppressed the clonogenicity in HCC cells. Furthermore, such downregulation in BACH1 or PDP1 could inhibit the PI3K-AKT-mTOR signaling. In conclusion, these reveal that BACH1 manifests a dominant tumor-promoting factor and is hence viewed as a promising therapeutic target of HCC, because it promotes HCC progression by targeting PDP1 towards PI3K-AKT-mTOR pathway activation.

bioengineering↗

bioRxiv2024

Simplified and Rapid Workflow Enhances Throughput of De Novo Sequencing of COVID-19 Neutralizing Antibodies

During the current COVID-19 pandemic, precise antibody sequencing is crucial for the rapid development of broad-spectrum or pan-{beta}-coronavirus neutralizing antibodies (NAbs) to prevent new variants of the coronavirus and other highly pathogenic {beta}-coronaviruses. However, mass spectrometry-based de novo sequencing remains challenging due to its high cost, low throughput, and unexpected missing of certain ion information. We developed an innovative approach using solely bottom-up to provide a rapid, robust, and refined solution for the current de novo sequencing challenges. The methodology, referred to as SP-MEGD for Single-Pot and Multi-Enzymatic Gradient Digestion, capitalizes on a five-protease gradient digestion by sampling every two hours for a total of 6 hours in an integrative reactor. The SP-MEGD method could engender numerous missed cleavage events and produce various peptide products of diverse lengths with overlapping stretches of residues, enabling efficient database-free de novo sequencing. Antibody assembly for single or mixed COVID-19-NAbs with publicly available sequences and commercial antibodies with unknown sequences was efficiently deciphered using our previously proposed optimization method, Fusion assembler. Our innovative study represents the first successful simultaneous discrimination and achieving over 99% accurate sequence coverage of a mixture containing three humanized COVID-19-NAbs (S2P6LH, BD5514LH, and BD5840LH). Furthermore, we utilized SP-MEGD and Fusion to sequence commonly used anti-CD8 and anti-CD4, and successfully confirmed their impact on immune cell clearance through in vivo experiments. Overall, our developed workflow demonstrates promise in facilitating the discovery and development of vaccines and antibody therapeutics while providing deeper insights into monoclonal antibodies (mAbs).

bioengineering↗

bioRxiv2023

Stanniocalcin 2 (STC2) is a potent biomarker of hepatocellular carcinoma with its expression being augmented in Nrf1α-deficient cells, but diminished in Nrf2-deficient cells

For insights into the fact that liver-specific knockout of Nrf1 leads to development of non-alcoholic steatohepatitis and spontaneous hepatoma, we previously found that loss of Nrf1 (i.e., a full-length isoform encoded by Nfe2l1) promotes HepG2-derived tumor growth in xenograft mice, but malgrowth of the xenograft tumor is significantly suppressed by knockout of Nrf2 (encoded by Nfe2l2). The mechanism underlying such marked distinctions in their pathologic phenotypes remains elusive, however, to date. Herein, we mined the transcriptome data of liver cancer from the TCGA database to establish a prognostic model of liver cancer and then calculated the predicted risk score of each cell line. The results indicated that knockout of Nrf1 significantly increased the risk score in HepG2 cells, whereas the risk score was reduced by knockout of Nrf2. Of note, stanniocalcin 2 (STC2, a biomarker of liver cancer, that is up-expressed in hepatocellular carcinoma (HCC) tissues with a reduction in the overall survival ratio of those patients) was augmented in Nrf1Nrf2-/- cells, but diminished in Nrf2-/- cells. Thereby, it is inferable that STC2 is likely involved in mediating the distinction between Nrf1Nrf2-/- and Nrf2-/-. Further investigation revealed that HIF1A is an upstream regulator of STC2 in caNrf2{Delta}N, rather than Nrf1Nrf2-/-, cells, and regulation of STC2 and HIF1A in Nrf1Nrf2-/- is determined by Nrf2, but the regulation of STC2 by Nrf2 may be independent on HIF1A. In turn, STC2 can regulate Nrf2 via the putative calcium-mediated Keap1-p62 signaling so to form a feedback regulatory loop. Such potential function of STC2 was further corroborated by a series of experiments combined with transcriptomic sequencing. The results unraveled that STC2 manifests as a dominant tumor-promoter, because the STC2-leading increases in clonogenicity of hepatoma cells and malgrowth of relevant xenograft tumor were almost completely abolished in STC2-/-cells. Together, these demonstrate that STC2 could be paved as a novel potent therapeutic target, albeit as a diagnostic marker, for hepatocellular carcinoma.

cell biology↗

bioRxiv2023

Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons

The expression of linear DNA sequences is precisely regulated by the three-dimensional (3D) architecture of chromatin. Morphine-induced aberrant gene networks of neurons have been extensively investigated; however, how morphine impacts the 3D genomic architecture of neuorns is still unknown. Here, we applied digestion-ligation-only high-throughput chromosome conformation capture (DLO Hi-C) technology to investigate the affection of morphine on 3D chromatin architecture of primate cortical neurons. After receiving continuous morphine administration for 90 days on rhesus monkeys, we discovered that morphine re-arranged chromosome territories, with a total of 391 segmented compartments being switched. Morphine altered over half of the detected topologically associated domains (TADs), most of which exhibited a variety of shifts, followed by separating and fusing types. Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops. Moreover, all identified differentially expressed genes (DEGs) from the RNA sequencing (RNA-seq) were mapped to the specific TAD boundaries or differential loops, and were further validated to be significantly changed. Collectively, an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated-morphine effects. Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.

bioinformatics↗

bioRxiv2020

LACCASE is Necessary for Root Development in Salvia miltiorrhiza

Laccases are multicopper-containing glycoproteins related to monolignol oxidation and polymerization. These properties indicate that laccases are involved in the formation of important medicinal phenolic acid compounds in Salvia miltiorrhiza such as salvianolic acid B (SAB), which is used for cardiovascular disease treatment. To date, 29 laccases have been found in S. miltiorrhiza, some of which influence the synthesis of phenolic acids. Because of the functional redundancy of laccase genes, their roles in S. miltiorrhiza are poorly understood. In this study, the CRISPR/Cas9 system was first used for dual gene locus targeting in S. miltiorrhiza to knock out multiple laccase family genes. The development of the roots was retarded, and root microstructure was abnormal in laccase mutant lines. Additionally, the accumulation of phenolic acid compounds as well as lignin was dramatically reduced. This study suggests that SmLACs are necessary for root development and phenolic acid compound metabolism in S. miltiorrhiza.

plant biology↗