Gene最新文献

Oral cancer (OC) has become increasingly prevalent in recent years, making it one of the most often occurring types of cancer in patients. The clinical identification of OC is usually a time-consuming procedure, and the outlook for individuals with OC is generally unfavorable, as no particular biomarkers have been established to far. The main risk factors linked to OC are high levels of tobacco and alcohol intake, together with a reduced occurrence of viral infections, such as human papillomavirus. Furthermore, there is evidence suggesting that genetic characteristics that can be passed down from parents to offspring play a role in increasing the likelihood of getting ovarian cancer. MicroRNAs (miRNAs) are brief RNA molecules that do not code for proteins and have the ability to either repress or promote the growth of tumors during cancer development. They have been discovered to control multiple signaling pathways within cells, and their abnormal regulation has been demonstrated to be crucial in initiating and furthering the development of cancer. Additionally, they have the ability to either facilitate or impede the entire multi-stage process of cancer metastasis, including epithelial-mesenchymal transition (EMT), migration, and invasion, by selectively targeting essential genes involved in these pathways. Several microRNAs have the ability to regulate gene expression through various ways. In addition, like other types of cancer, OC has shown alterations in the expression of miRNAs, and certain miRNAs may have the ability to be used for diagnosis and treatment. The investigation of these miRNA could perhaps result in advancements in the specified instances of OC.

Gordonia spp. are Gram-positive, non-sporulating bacteria which have several industrial as well as environmental applications. In order to enhance their potential, metabolic engineering is required which often involves genome manipulation. For this purpose, temperature sensitive plasmids are useful as the desired genes for integrases or recombinases can be supplied transiently, followed by curing of the plasmid. Here, we report the construction of a cloning vector and temperature sensitive vectors based upon the pKB1 replicon from Gordonia westfalica. The amino acid residues or regions for creating temperature sensitive mutants were predicted based on in silico methods, and the dynamics of these mutant proteins were studied using docking and molecular dynamic simulations. The desired mutations were incorporated in the replication protein by site directed mutagenesis. The results were validated by growth kinetics of the wild type and mutants at permissive and non-permissive temperatures. This is the first report on temperature sensitive vectors based on native replicon from a plasmid originating from Gordonia.

Alexander disease (AxD), an autosomal dominant leukodystrophy, is caused by mutations in the GFAP, the gene encoding glial fibrillary acidic protein (GFAP). The disease, classified by age of onset into infantile, juvenile, and adult forms, is characterized by white matter degeneration and astrocytic inclusions called Rosenthal fibers. A patient underwent clinical, radiological, and molecular analyses to confirm a suspected diagnosis of AxD. The functional effect of the variant identified was tested using computational tools and in HeLa and astrocytoma cell lines. We report a case of juvenile AxD that clinically developed acute respiratory distress due to bilateral vocal cord paralysis. Brain and spinal cord MRI revealed the typical findings of the disease, including bulbospinal atrophy and T2-weighted hyperintensities in the frontal periventricular white matter. Molecular genetic testing identified a novel de novo c.713 T > G (p.I238S) variant of GFAP. In silico analyses revealed that the variant at evolutionarily conserved residue likely affects protein function. In vitro assays confirmed its pathogenic effect, showing that p.I238S protein expression significantly associates with aggregate formation in cellular models. Extending the clinical and molecular characterization of new cases of AxD is an important achievement to better characterize the disease.

Cell elongation is an important process during cotton fiber development, ultimately determining the length of mature fibers. Myo-inositol oxygenase (MIOX) pathway provides pivotal precursors for the synthesis of non-cellulosic polysaccharides in plant cell walls. However, the role of MIOX gene in cotton fiber development has not been reported. Here, we hypothesized that Gossypium barbadense MIOX gene GbMIOX8 (GbM_D05G1480.1) could regulate fiber length by modulating cell wall composition. To test this hypothesis, we characterized the functional properties of GbMIOX8. GbMIOX8 preferentially expressed during fiber initiation and elongation in cotton and encodes non-secretory protein targeted to the cytoplasm. Overexpression of GbMIOX8 afforded transgenic A. thaliana significantly longer leaf trichomes, as well as longer hypocotyl cells compared to the wild type, with increases of at least 11 % and up to 23 %. We further overexpressed GbMIOX8 in cotton and found that transgenic cotton displayed fiber length that was increased by an average of 1.61 mm in the T₁ generation and 1.93 mm in the T₂ generation, respectively. Similar to Arabidopsis, transgenic cotton exhibited at least a threefold increase in myo-inositol oxygenase activity and content, boosting glucuronic acid production and reducing inositol. Furthermore, pectin and cellulose contents rose in transgenic cottons, with average rises of 19 % and 38 % respectively, indicating enhanced biosynthesis of these two cell wall components. These results revealed that GbMIOX8 played an important role in the elongation of plant cells by altering cell wall components and could be valuable for cotton fiber quality improvement.

Breast cancer, which is the most common cancer among women in Türkiye and throughout the world, is also one of the leading causes of cancer-related deaths. A significant factor in these deaths is metastatic breast cancer, which spreads to distant organs. The metastasis of the breast tumor follows a series of steps. Many proteins and signal molecules are in charge of these processes. In addition, NEAT1, a long noncoding RNA (lncRNA), was reported to play a key role in breast cancer cell proliferation and survival. Numerous cancer kinds were also shown to have extraordinary miR-410-3p expression levels. NEAT1 and miR-410-3p expression patterns in MCF-7 and MCF-10A cell lines were investigated using quantitative real-time polymerase chain reaction (qRT-PCR) in this study. The results demonstrated that NEAT1 was elevated by 2.30-fold in cancer cells in comparison to normal cells, whereas miR-410-3p was diminished by -2.85-fold. Furthermore, the transwell invasion experiment demonstrated the invasive potential of the MCF-7 cell line, whereas the MCF-10A cells could not invade. The target analysis revealed that functions of the targets were associated with biological adhesion and cel growth. In conclusion, a correlation was found between overexpression of NEAT1 and increased invasiveness of target cells, as well as inhibition of miR-410-3p, which is a regulatory target of NEAT1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, and mutations in the NF1 gene lead to RAS overactivation, which stimulates abnormal cell proliferation and can cause various tumors. The c.1748A > G mutation in the NF1 gene was initially classified as a missense mutation, but has also been suggested to be a splice mutation. It is thought that the substitution of A for G generates a cryptic splice site, resulting in a 27 bp deletion in the mRNA transcript, but this conclusion has not been documented in currently available databases. The present study was conducted to establish whether the NF1 c.1748A > G mutation induces a splicing error, and to determine whether it is pathogenic i.e. activates RAS and increases the expression of NF1-related downstream signaling molecules. We have confirmed by RT-PCR analysis of NF1 transcripts produced in the patient's peripheral blood lymphocytes as well as in a minigene construct and in iPSCs harboring the c.1748A > G mutation that this mutation creates a cryptic splice site which has the effect of deleting the first 27 bases of exon 16, and leading to transcriptional haploinsufficiency. Additionally, NPCs expressing the splicing mutant exhibited increased phosphorylation of NF1-related AKT/mTOR and Raf/MEK/Erk, as well as more effective wound healing and chemotaxis. We conclude that the NF1 c.1748A > G mutation acts as a splice mutation forming a novel cryptic site, causing a 27 bp deletion in the mRNA. This leads to increased expression of NF1-related downstream signaling molecules through RAS activation, inducing cell proliferation and potential tumor formation.