Biology subjects

Kong, P.

Publications and source records attributed to Kong, P..

5 recordsLinked to original sources

bioRxiv2025

Expression of β-catenin, LEF-1, MMP7 and SFRP5 associated with poor outcome in pancreatic cancer

Pancreatic cancer is highly aggressive and lethal malignancies worldwide. {beta}-catenin, LEF-1, MMP7 and SFRP5 are key regulatory proteins in the Wnt signaling pathway. It has been confirmed that Wnt signaling pathway is involved in the biological regulation of pancreatic cancer cells and plays an important role. However, its effect on the malignant phenotypes of pancreatic cancer cell and the corresponding molecular details remains unknown. In the current study, the expression of {beta}-catenin, LEF-1 and MMP7 was up-regulated and the expression of SFRP5 was down-regulated in pancreatic cancer cell lines and tissues by RNA sequencing, quantitative PCR (qPCR) and immunohistochemical analysis. {beta}-catenin, LEF-1 and MMP7 positive expression correlates with poor prognosis in PDAC patients, and SFRP5 positive expression correlates with longer survival times. Subsequently r software was used to establish a rosette model to predict the prognosis of pancreatic cancer according to the results of multi-factor analysis. After statistical analysis, age, CA-199, {beta}-catenin, MMP7 and SFRP5 could serve as promising biomarkers for predicting prognosis in PDAC patients. This study also suggests that survival probability of patients can be reliably predicted by a nomogram-based method.

cancer biology↗

bioRxiv2025

Metabolic basis of the astrocyte-synapse interaction governs dopaminergic-motor connection

Perisynaptic astrocyte processes are constitutive attachments of synapses in the central nervous system. However, the molecular mechanisms that control perisynaptic astrocyte ensheathment and their implications in the wiring of neural circuits remain unclear. Here, we report that glycolysis controls astrocyte-synapse contact. In the Drosophila larval dopaminergic (DAergic) circuit, blocking astrocyte glycolysis stimulated perisynaptic ensheathment by attenuating astrocyte-to-DAergic neuron neuroligin 2-neurexin 1 signaling. As a result, the larvae executed more reorientation actions during locomotion. At the circuit level, behavioral alterations were found to arise from increased DAergic neuronal synaptogenesis and DAergic-motor connection. Our research uncovers an ancient metabolic basis that determines perisynaptic astrocyte ensheathment abundance through a conserved neuroligin-neurexin signaling pathway and demonstrates the role of astrocyte glycolysis in controlling DAergic-motor circuit assembly and function.

neuroscience↗

bioRxiv2024

The Alzheimers Disease Risk Genes MS4A4A And MS4A6A Cooperate to Negatively Regulate Trem2 and Microglia states

Genetic variations in MS4A4A and MS4A6A are linked to the regulation of cerebrospinal fluid soluble TREM2 (sTREM2) levels and are associated with Alzheimers disease (AD) risk and progression. Using CRISPR knockout and MS4A4A-degrading antibodies in primary human microglia, non-human primates (NHP), and a xenotransplantation model of amyloid pathology, we provide evidence that MS4A4A and MS4A6A are negative regulators of both the transmembrane and soluble TREM2 proteins. They also negatively regulate microglia proliferation, survival, metabolism, lysosomal function, energetics, phagocytosis, and disease-fighting states. Mechanistically, we find that MS4A4A exerts negative regulation by interacting with MS4A6A and protecting it from degradation. MS4A6A in turn forms a complex with and blocks the co-receptor DAP12, which is required for the stability, cell surface localization, and signaling of TREM2 and other receptors. Taken together, the data indicate that MS4A4A and MS4A6A are cooperating, post-transcriptional negative regulators of TREM2 and microglial function, and potential drug targets for AD.

neuroscience↗

bioRxiv2022

Elevated FAM84B promotes cell proliferation via interacting with NPM1 in esophageal squamous cell carcinoma

Family with sequence similarity 84, member B (FAM84B) is a significant copy number amplification gene in the 8q24.21 locus identified by our previous WGS study in esophageal squamous cell carcinoma (ESCC). However, its clinical relevance and potential mechanisms have been elusive. Here, we performed the association analyses between FAM84BAmp and clinicopathological features using our dataset with 507 ESCC samples. The results indicated that, compared with the FAM84Bnon-Amp patients, the FAM84BAmp patients showed a more aggressive and a worse prognosis. Significant correlation was discovered between the expression level of FAM84B and FAM84BAmp in ESCC cohort. Furthermore, we found that the forced expression change of FAM84B can influence ESCC cell proliferation and cell cycle status, which is probably mediated by NPM1. A direct interaction between FAM84B and the C-terminal (189-294aa) of NPM1 was identified, which increased the NPM1 nuclear expression. Over-expression of NPM1 could inhibit the CDKN2A protein expression, which might affect the ESCC cell cycle. Our results indicate FAM84B CNA may be a potential diagnostic and therapeutic biomarker in ESCC, meanwhile, reveal a novel mechanism of FAM84B that it promotes tumorigenesis via interacting with NPM1 and suppressing CDKN2A.

cancer biology↗

bioRxiv2020

Helicobacter pylori accelerates KRAS-dependent gastric dysplasia

More than 80% of gastric cancer is attributable to stomach infection with Helicobacter pylori (Hp), even though the bacterium is not always present at time of diagnosis. Infection is thought to lead to cancer by promoting the accumulation of oncogenic mutations downstream of inflammation; once oncogenic pathways become activated, infection may become dispensable for cancer development. Gastric preneoplastic progression involves sequential changes to the tissue, including loss of parietal cells, spasmolytic polypeptide-expressing metaplasia (SPEM), intestinal metaplasia (IM) and dysplasia. In mice, active KRAS expression recapitulates these tissue changes in the absence of Hp infection. This model provides an experimental system to investigate whether Hp infection has additional roles in preneoplastic progression, beyond initiating inflammation. Mice were assessed by evaluating tissue histology, gene expression changes, the immune cell repertoire, and expression of metaplasia and dysplasia markers. Compared to Hp-/KRAS+ mice, Hp+/KRAS+ mice had i) severe T cell infiltration and altered macrophage polarization; ii) altered expression of metaplasia markers, including increased expression of CD44v9 (SPEM) and decreased expression of TFF3 (IM); iii) more dysplastic (TROP2+) glands; and iv) greater proliferation of metaplastic and dysplastic glands. Hp was able to persistently colonize the stomach during the onset of these tissue changes, and eradication of Hp with antibiotics prevented metaplastic, dysplastic and proliferation marker changes. Collectively, these results suggest that gastric preneoplastic progression differs between Hp+ and Hp-cases, and that sustained Hp infection can promote the later stages of gastric preneoplastic progression, in addition to its established role in initiating chronic inflammation.

cancer biology↗