Molecular Biology Reports最新文献

Colorectal cancer (CRC) is the third most frequent cancer worldwide. It is the second leading cause of cancer-related death, affecting both men and women. It has been described that 20-25% of colorectal tumors have mutations in the PIK3CA gene, mainly in three hotspots: E542 and E545 and H1047. The aim of this study was to compare the prevalence of PIK3CA gene mutations in colorectal tumors based on a systematic review of a selection of studies. Nighty seven studies enrolling 48,446 patients were eligible for inclusion. Most studies were conducted in Asian (41.2%) and European countries (34.0%). The global prevalence ranged from 0 to 80%, with a mean prevalence of 13.7%. Fourteen studies reported a prevalence of less than 5%, 22 between 5 and 10%, 32 between 10 and 15% and 29 showed a prevalence of more than 15%. Mutations were more common in exon 9 than in exon 20 (9.5% vs. 4.7%). After discussing a number of possible reasons that could explain the differences in prevalence, it is very hard to deduce which is the main factor influencing the observed frequency.

Background: Farnesyltransferase inhibitors (FTIs) were developed for preventing the prenylation of aberrant Ras in human cancer. Furthermore, prenylation is involved in multiple biological processes and plays a putative role in signalling pathways such as the Ras-mitogen-activated-protein kinase (MAPK) pathway. Matrix-vesicle-mediated mineralization (MVM) is the first step in the development of eukaryotic mineralized tissue. In this study, we evaluated the effect of FTIs on MVM in the osteosarcoma cell line SaOS-2 and elucidated the role of farnesylation in this process.

Methods: SaOS-2 cells were treated with the FTIs Lonafarnib and Tipifarnib. Mineralization was assessed using Alizarin Red S staining. Enzyme assays were conducted to measure alkaline phosphatase (ALP) activity. Western blot analysis and Oxford Nanopore sequencing were performed to evaluate the expression of ALP, collagen type I (COL1A1), and Runt-related transcription factor 2 (RUNX2).

Results: Inhibition of farnesylation by FTIs resulted in decreased mineralization, as evidenced by reduced Alizarin Red S staining. Additionally, RUNX2 activity was diminished, leading to a reduction in MVM and decreased expression of ALP and COL1A1.

Conclusion: Our findings demonstrate that FTIs Lonafarnib and Tipifarnib impair MVM, highlighting the essential role of farnesylation in biomineralization.

Methyltransferase-like protein 3 (METTL3) functions as the primary "writer" of N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes. Functionally, METTL3 regulates a broad spectrum of cellular processes, including cell cycle progression, proliferation, apoptosis, invasion, migration, and differentiation. In colorectal cancer, METTL3 expression is frequently upregulated and has been correlated with poor prognosis. Therefore, this review attempts to organize and describe the main molecular and cellular mechanisms through which METTL3 drives colorectal cancer. Mechanistically, METTL3 contributes to tumor growth, metastatic dissemination, and the development of resistance to chemotherapy and radiotherapy. Special emphasis is placed on the clinical relevance of METTL3, not only as a biomarker, but also as a potential therapeutic target. Less explored topics are also addressed, such as the interaction between METTL3 and gut microbiota. Altogether, this review underscores the multifaceted role of METTL3 in colorectal cancer and the importance of further investigation to translate these insights into clinical applications.

Background: Whole Exome sequencing (WES) is emerging as the primary diagnostic strategy for chronic kidney disease (CKD), a major public health concern, and its diagnostic yield is dependent on the patient selection criteria and techniques used.

Methods: This study aimed to investigate molecular defects in patients with clinically suspected monogenic CKD using WES. A total of 160 pediatric and adult patients presenting with diverse chronic kidney disorders were enrolled; 134 were subjected to WES analysis.

Results: WES identified genetic causes in 89 patients, with a diagnostic yield of 66.4%. A total of 55 variants were characterized among our CKD patients, including 45 different pathogenic or likely pathogenic variants and ten variants of uncertain significance. The diagnostic yield for the pediatric group was 76.4%, which was greater than that of the adult group (23.6%). Among the 89 patients, the molecular diagnosis aligned with the initial clinical findings in 63 patients (70.7%), refined the clinical diagnosis in five patients (5.6%), and led to a complete reclassification of the original diagnosis in 21 patients (23.6%).

Conclusions: Our findings demonstrate the robust diagnostic and clinical genetic value of WES in a broad spectrum of kidney diseases.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is characterized by the BCR::ABL1 fusion gene resulting from the translocation t(9;22). This type of leukemia represents a biologically and clinically distinct subset of ALL, known for its aggressive nature and comparatively poor prognosis among hematologic malignancies. Although the advent of tyrosine kinase inhibitors (TKIs) has converted the therapeutic view and fulfilled short-term outcomes, resistant responses remain limited, and disease relapse, often due to BCR::ABL1 kinase domain mutations or activation of alternative signaling pathways, continues to impede long-term success. Recent findings emphasizes the essential involvement of microRNAs in leukemogenesis, TKI resistance, and the advancement of Ph+ ALL. Importantly, miR-17∼92 cluster members (such as miR-17, miR-18a, miR-20a) can prompt apoptosis by direct suppression of BCL2 in BCR::ABL1 positive cells. Moreover, epigenetic silencing of miR-203 enhances BCR::ABL1 expression, further contributing to TKI resistance. These small regulatory RNAs consequently act for promising candidates both as therapeutic targets and as prognostic biomarkers, with the potential to fill treatment gaps that persist even in the TKI era.

Background: The lesser grain borer, Rhyzopertha dominica (F.), is a major pest of stored grains, and its resistance to phosphine fumigant poses a significant challenge to grain storage management in India. Mutations in the dihydrolipoamide dehydrogenase (dld) gene have been associated with phosphine resistance in this pest.

Methods and results: This study investigated phosphine resistance in 15 field populations of R. dominica collected across north and northeastern India. Discriminating dose bioassays classified the populations into strong and weak resistant categories. Resistance genotyping was conducted using cleaved amplified polymorphic sequence (CAPS) markers, and phylogenetic analysis revealed a predicted clustering pattern between strong and weak resistant populations. A total of 14 variants were identified in the dld gene, with the Y3C variant being the most prevalent, followed by P49S and E69K. Strongly resistant populations predominantly carried both Y3C and P49S mutations. The population from Kota was found to harbor a significantly higher number of uncharacterized mutations.

Conclusion: The findings indicate a widespread presence of phosphine resistance among R. dominica populations in India, driven largely by specific mutations in the dld gene. These insights highlight the need for resistance monitoring and management strategies to mitigate the spread of phosphine resistance in stored grain pests.

Bovine leukemia virus (BLV), a member of the Deltaretrovirus genus, causes enzootic bovine leukosis, leading to clinical outcomes that range from asymptomatic infection to malignant lymphoma. Host genetic factors significantly influence BLV susceptibility, proviral load (PVL), immune response, and disease progression. This mini-review synthesizes evidence on genetic polymorphisms in immune-related genes such as BoLA-DRB3, Tumor necrosis factor (TNF), and immunoglobulin loci, and examines novel findings from genome-wide association studies (GWAS). Beyond classical immune genes, recent GWAS have identified novel loci including SPATA16 (spermatogenesis associated 16), ABT1 (activator of basal transcription 1), IER3 (immediate early response 3), Adaptor Related Protein Complex 4 Subunit Beta 1 (AP4B1), Tripartite Motif Containing 45 (TRIM45), Patatin Like Phospholipase Domain Containing 1 (PNPLA1), and PRRC2A (proline-rich coiled-coil 2 A) that are implicated in transcriptional regulation, stress response, RNA processing, and intracellular transport, all of which may modulate viral replication and persistence. Understanding these genetic determinants provides new insights into host-virus interactions and offers opportunities for selective breeding strategies, biomarker development, and improved BLV control programs.

Male sterility is a vital trait exploited in hybrid seed production to boost crop yield and improve quality. In rice, different male sterility systems have been developed, significantly advancing the production of high-yielding hybrids. The three main types of male sterility in rice are cytoplasmic male sterility (CMS), photoperiod-sensitive genic male sterility (PGMS), and genic male sterility (GMS). Among these, CMS is the most widely used, arising from interactions between mitochondrial (cytoplasmic) and nuclear genes, resulting in pollen dysfunction. PGMS, on the other hand, is influenced by environmental cues such as day length and temperature, while GMS is attributed to mutations in specific nuclear genes affecting anther or pollen development. A thorough understanding of the genetic and molecular mechanisms underlying these systems is essential for efficient hybrid rice breeding. CMS lines are typically crossed with maintainer and restorer lines carrying fertility-restoring genes to produce fertile F₁ hybrids. Recent advancements in molecular biology, genomics, and genome editing technologies have accelerated the development of novel male-sterile and fertility-restoring lines, thereby enhancing the precision and scalability of hybrid breeding programs. These innovations are not only expanding the genetic base of hybrid rice but also making the production process more sustainable. As global food demand rises alongside climate uncertainties, the strategic use of male sterility in rice breeding holds immense potential for improving agricultural productivity.