The neuroendocrine system is a complex biological system controlled by various neuropeptides and hormones. The evolution and network properties of neuroendocrine genes are analyzed along with their expression profiles. The neuroendocrine genes show very similar expression profiles and local network properties across a wide range of tissues consistent with the physiological roles of their proteins. Moreover, the coordinated evolution of 10 neuroendocrine genes involved in mammalian reproduction and homeostasis is demonstrated using several methods, such as correlated evolution, relative-rate test, relative-ratio test and codon usage bias. The neuroendocrine genes seem to evolve predominantly under similar selective strengths and regimes of purifying selection, which is well reflected in their evolutionary fingerprints. This result demonstrates for the first time a key role of natural selection in creating and maintaining a well-designed neuroendocrine system at the genomic level. It also indicates that component properties of a complex system at a higher physiological scale may determine component properties at a lower genomic scale and/or vice versa.
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http://dx.doi.org/10.1039/c2ib20081c | DOI Listing |
J Transl Med
January 2025
Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Small cell neuroendocrine cervical carcinoma is a highly aggressive tumor characterized by early metastasis, a high recurrence rate, and poor prognosis. This study represents the first instance of single-cell sequencing conducted on small cell neuroendocrine carcinoma of the cervix worldwide. Analysis of gene expression regulatory networks revealed that the transcription factor TFF3 drived up-regulation of ELF3.
View Article and Find Full Text PDFChromosomal instability (CIN) is common in solid tumours and fuels evolutionary adaptation and poor prognosis by increasing intratumour heterogeneity. Systematic characterization of driver events in the TRACERx non-small-cell lung cancer (NSCLC) cohort identified that genetic alterations in six genes, including FAT1, result in homologous recombination (HR) repair deficiencies and CIN. Using orthogonal genetic and experimental approaches, we demonstrate that FAT1 alterations are positively selected before genome doubling and associated with HR deficiency.
View Article and Find Full Text PDFMol Med
December 2024
Medical Oncology Translational Research Lab, Jilin Cancer Hospital, Changchun, 130012, China.
Background: Small cell lung cancer (SCLC) is a highly fatal malignancy, the complex tumor microenvironment (TME) is a critical factor affecting SCLC progression. Cancer-associated fibroblasts (CAFs) are crucial components of TME, yet their role in SCLC and the underlying mechanisms during their interaction with SCLC cells remain to be determined.
Methods: Microenvironmental cell components were estimated using transcriptome data from SCLC tissue available in public databases, analyzed with bioinformatic algorithms.
Cancer Metab
December 2024
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, 200 First St. SW, Rochester, MN, 55905, USA.
Heterozygosity for loss-of-function alleles of the genes encoding the four subunits of succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD), as well as the SDHAF2 assembly factor predispose affected individuals to pheochromocytoma and paraganglioma (PPGL), two rare neuroendocrine tumors that arise from neural crest-derived paraganglia. Tumorigenesis results from loss of the remaining functional SDHx gene copy, leading to a cell with no functional SDH and a defective tricarboxylic acid (TCA) cycle. It is believed that the subsequent accumulation of succinate competitively inhibits multiple dioxygenase enzymes that normally suppress hypoxic signaling and demethylate histones and DNA, ultimately leading to increased expression of genes involved in angiogenesis and cell proliferation.
View Article and Find Full Text PDFBMC Cancer
December 2024
Department of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Background: Medullary Thyroid Carcinoma (MTC) is closely associated with mutations in the RET proto-oncogene, placing the activated RET protein at the center of MTC pathogenesis. Existing therapeutic solutions, primarily tyrosine kinase inhibitors such as selpercatinib, vandetanib, and cabozantinib, have shown moderate efficacy but are accompanied by increased risks of side effects and resistance. This study unveils a promising avenue using nonactin, a compound historically recognized for its antibacterial properties, targeting the G-quadruplex interactions within the RET proto-oncogene.
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