Although several biomarkers have been identified to predict the prognosis of lower-grade (Grade II/III) gliomas (LGGs), we still need to identify new markers to facilitate those well-known markers to obtain more accurate prognosis prediction in LGGs. Bioinformatics data from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Cancer Cell Line Encyclopedia (CCLE) datasets were used as the research materials. In total, 34 genes associated with the HIF1A pathway were analyzed using the hierarchical method to search for the most compatible gene. The BICD cargo adaptor 1 (BICD1) gene () was shown to be significantly correlated with The hypoxic inducible factor 1A (HIF1A) expression, the World Health Organization (WHO) grade, and mutation status. In addition, downregulation was significantly correlated with a higher Karnofsky performance score (KPS), // mutations, wild-type and younger patient age in the enrolled LGG cohort. Moreover, expression was significantly upregulated in wild-type LGGs with mutations. Kaplan-Meier survival analysis revealed that downregulation predicts a favorable overall survival (OS) in LGG patients, especially in those with mutations. Intriguingly, we found a significant correlation between downregulation and a decreased level of , , , or in LGGs. Our findings suggest that BICD1 downregulation could be a potential biomarker for a favorable prognosis of LGGs.
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http://dx.doi.org/10.3390/biology10080701 | DOI Listing |
The folded auto-inhibited state of kinesin-1 is stabilized by multiple weak interactions and binds weakly to microtubules. Here we investigate the extent to which homodimeric kinesin-1 lacking light chains is activated by the dynein activating adaptor BicD. We show that one or two kinesins can bind to the central region of BicD (CC2), a region distinct from that which binds dynein-dynactin (CC1) and cargo-adaptor proteins (CC3).
View Article and Find Full Text PDFCytoplasmic dynein is an essential microtubule motor protein that powers organelle transport and mitotic spindle assembly. Its activity depends on dynein-dynactin-cargo adaptor complexes, such as dynein-dynactin-BicD2 (DDB), which typically function with two dynein motors. We show that mechanical tension recruits a third dynein motor via an auxiliary BicD adaptor binding the light intermediate chain of the third dynein, stabilizing multi-dynein assemblies and enhancing force generation.
View Article and Find Full Text PDFGenetics
April 2024
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
In the fruit fly Drosophila melanogaster, two cells in a cyst of 16 interconnected cells have the potential to become the oocyte, but only one of these will assume an oocyte fate as the cysts transition through regions 2a and 2b of the germarium. The mechanism of specification depends on a polarized microtubule network, a dynein dependent Egl:BicD mRNA cargo complex, a special membranous structure called the fusome and its associated proteins, and the translational regulator orb. In this work, we have investigated the role of orb and the fusome in oocyte specification.
View Article and Find Full Text PDFNat Struct Mol Biol
March 2024
Developmental Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Dynein and kinesin motors mediate long-range intracellular transport, translocating towards microtubule minus and plus ends, respectively. Cargoes often undergo bidirectional transport by binding to both motors simultaneously. However, it is not known how motor activities are coordinated in such circumstances.
View Article and Find Full Text PDFJ Cell Sci
January 2024
Institute of Cell Biology, University of Bern, CH-3012 Bern, Switzerland.
Cell polarization requires asymmetric localization of numerous mRNAs, proteins and organelles. The movement of cargo towards the minus end of microtubules mostly depends on cytoplasmic dynein motors. In the dynein-dynactin-Bicaudal-D transport machinery, Bicaudal-D (BicD) links the cargo to the motor.
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