Journal of Gene Medicine最新文献

Claudin-1 (CLDN1), a vital tight junction protein, is linked to epithelial-mesenchymal transition (EMT) of tumor cells. In this study, multi-omics including expression profiles of colorectal cancer (CRC) from The Cancer Genome Atlas (TCGA) dataset, colon expression profiles from the Genotype-Tissue Expression (GTEx) database, and the expression profiles from the Gene Expression Omnibus (GEO) dataset GSE251845 were combined and analyzed. We screened for differentially expressed genes (DEGs) in CRC and identified 218 intersected genes related to EMT. Then, deep machine learning models, including least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machine (SVM), were applied in depth screening, and 11 candidate genes were ultimately screened, including ADAM12, CD36, CLDN1, ETV4, FOXQ1, GLIPR2, MMP11, MMP7, NCL, SALL4, and SIM2. Functional annotation revealed that CLDN1 is closely associated with the AMP-activated protein kinase (AMPK) and lipid metabolic pathways. Our validation experiments showed that CLDN1 was upregulated in human CRC tissues and cell lines compared with adjacent normal tissues and normal cell lines, and it promoted CRC cell proliferation, EMT, and lipid metabolism in vitro. Furthermore, administration of Compound C, an AMPK inhibitor, reversed the suppressive effects of CLDN1 knockdown on cell proliferation, EMT, and lipid metabolism, indicating the AMPK signaling pathway is involved in CLDN1-mediated EMT and lipid metabolism in CRC cells. These findings suggest that CLDN1 plays a significant role in EMT and lipid metabolism of CRC cells and can be utilized as a therapeutic target for CRC.

Idiopathic interstitial pulmonary fibrosis (IPF) is a chronic and progressive disease characterized by interstitial fibrosis, with poor prognosis and high mortality. TRIM34 is involved in the intracellular ubiquitination process, but its mechanism of action in IPF is currently unknown. The purpose of this study was to investigate the effect of TRIM34 on the IPF process and its mechanism. In this study, 5 mg/kg of bleomycin (BLM) was injected into the rat trachea to construct the IPF animal model, and 10 ng/mL of VEGF165 was added to human pulmonary microvascular endothelial cell (HPMECs) culture medium to construct the angiogenic cell model. The expression of proteins was detected by Western blot. The assessment of proliferation, angiogenesis, and fibrosis in HPMECs and rat lung tissue was conducted using EdU staining, scratch tests, angiogenesis tests, HE staining, and Masson staining. The research indicated a reduction in TRIM34 expression in IPF. Overexpression of TRIM34 significantly improved pulmonary inflammatory infiltration in IPF rats, restored alveolar structure, reduced collagen deposition in lung tissue, upregulated the expression of E-cadherin, downregulated the expression of COL-I, COL-III, a-SMA, CD31, CD34, and VEGFA, and finally alleviated the progression of IPF in rats. In addition, overexpression of TRIM34 also inhibited VEGF-induced proliferation, migration, and angiogenesis of HPMECs by inhibiting glucose uptake and pyruvate, lactic acid, and ATP content of HPMECs. In terms of mechanism, Tianlongjie (TL) therapy promotes HIF-1A ubiquitination degradation by upregulating TRIM34 expression, thereby inhibiting glycolysis, reducing angiogenesis, and alleviating IPF progression. In conclusion, TL therapy inhibits angiogenesis by upregulating TRIM34 expression and ultimately alleviates IPF progression.

Osteoarthritis (OA) is a degenerative condition of bone characterized by loss of cartilage, subchondral bone sclerosis, osteophyte growth, synovial inflammation, and influenced by biomechanical loading. The loss of articular cartilage is the primary concern of OA, while subchondral bone plays a crucial role in the integrity of articular cartilage, providing mechanical support and nutrition supply and constantly adapting to the changing biomechanical environment in weight-bearing joints. Osteocytes, abundant in subchondral bones, sense mechanical loading and control bone adaptive remodeling. Their bodies reside in lacunae and dendritic projections pass through tiny channels named canaliculi, together forming the lacunar–canalicular system (LCS). The disorganization of osteocyte and LCS disrupts communication between osteocytes and other cells; it may contribute to OA initiation and or progression. In this review, insights into osteocyte as the master regulator of mechanosensation and mechanotransduction in bone remodeling by its mechanosensitive structures and dysregulation of osteocyte and LCS-specific genes in OA are discussed. Finally, this review highlights emerging genetic and molecular targets, including Kindlin-2, PIEZO1, and Netrin-1, and discusses their potential in developing novel therapies. By integrating recent advances in mechanobiology, RNA-based therapies, and nanotechnology, we propose a multi-targeted approach to improve OA therapeutics. This review provides a comprehensive framework for understanding OA pathogenesis and identifies promising avenues for future research.

Moyamoya disease (MMD) is a rare degenerative stenosis and occlusive cerebrovascular illness. It is characterized by cerebral ischemia and/or cerebral hemorrhage as the two main clinical signs. It is a common cause of stroke in both children and adults. Several recent studies illustrated the crucial role of microRNAs (miRNAs) in the pathophysiology of MMD via the regulation of endothelial cells and smooth muscle cells. Furthermore, other studies highlighted the decisive role of miRNAs in the underlying molecular pathophysiological mechanisms in MMD via regulation of cellular proliferation, angiogenesis, extracellular matrix remodeling, and vascular inflammation. This review aims to explore the involvement of miRNAs in MMD pathogenesis and to assess their potential use as biomarkers for stroke risk and their utility as therapeutic targets for the treatment of MMD.

The airway epithelium is the primary target of the trachea in lung transplant rejection and epithelial cell injury are frequently observed in lung transplants. Farnesyl pyrophosphate synthase (FPPS), a pivotal enzyme in the mevalonate pathway, synthesizes isoprenoid compounds like FPP and GGPP. This study found upregulated expression of FPPS in the epithelial cells of the tracheal transplant rat model and the use of the FPPS inhibitor zoledronic acid reduced the tracheal epithelial cell damage. Using CRISPR/CAS9, FPPS was knocked down in pulmonary-derived epithelial cells, and RNA sequencing analysis revealed alterations in the gene expression profile, notably involving significant reductions in multiple endoplasmic reticulum stress-related genes, including the ATF4/TRIB3 pathway and the ERN1/XBP1 pathway, which were further confirmed at the protein level. Additionally, treatment with zoledronic acid exhibited inhibitory effects on endoplasmic reticulum stress in the tracheal transplant rat model. Furthermore, FPPS knockdown and Inhibition were found to suppress the expression of multiple amino acid transporters, including SLC7A5, resulting in decreased intracellular levels of multiple amino acids, reduced mTORC1 pathway activity, and enhanced autophagic function. In summary, this study identified the protective roles of FPPS inhibition in epithelial cells of the tracheal transplant model, potentially mediated through reductions in endoplasmic reticulum stress, decreased mTORC1 activity, and augmented downstream autophagic processes.

Renal cell carcinoma (RCC) is a malignant neoplasm arising from the renal epithelium and constitutes approximately 2% of global cancer diagnoses and mortalities. With increasing prevalence, RCC remains a pressing clinical challenge, particularly because of its resistance to conventional therapies and poor outcomes in advanced stages. Long noncoding RNAs (lncRNAs) have been proposed as key molecular mediators in RCC, orchestrating critical pathways such as epithelial-to-mesenchymal transition (EMT), cellular proliferation, apoptosis, angiogenesis, and metastasis. Their roles in therapeutic resistance, including chemoresistance and radioresistance, further highlight their impact on treatment outcomes. Additionally, the potential of natural compounds such as curcumin, quercetin, and resveratrol to target lncRNA-mediated pathways has garnered attention, offering insights into novel therapeutic strategies. This review examines the biogenic pathways and multifaceted functions of lncRNAs, shedding light on their influence on RCC pathophysiology and posttranscriptional regulation. In addition, this review emphasizes the repercussions of natural compounds as lncRNA-targeted therapies, thus offering a comprehensive perspective on emerging strategies that may lead to more effective and personalized treatments.