Journal of cellular biochemistry最新文献

tRNA-derived fragments (tRFs) are a newly recognized class of small noncoding RNAs (sncRNAs) that play significant roles in various diseases. The Wnt pathway plays a key role in various physiological processes such as embryonic development, tissue renewal and regeneration. In the regulation of Wnt/β-catenin, Forkhead box k1(FOXK1), Frizzled class receptor 3 (FZD3), and Wnt5b can be targeted and inhibited by three tRFs: tRF3008A targets FOXK1 to inhibit colorectal cancer (CRC), 5′-tiRNAVal targets FZD3 to inhibit breast cancer (BrC), and tRF-22-8BWS7K092 targets Wnt5b to induce ferroptosis in lung cells. Additionally, tRF-24-V29K9UV3IU can inhibit the levels of FZD3, Van Gogh-like protein 1 (VANGL1), and cyclin D2 (CCND2) through an unexplained mechanism and play a role in inhibiting gastric cancer (GC). Clinical data has shown that the expression levels of certain tRFs are associated with the prognosis and pathological features of CRC and BrC patients. Low expression of tRF3008A is associated with poor prognosis and adverse pathological features in CRC patients, while high expression of tiRNA-Phe-GAA-003 and low expression of 5′-tiRNAVal are associated with poor prognosis and adverse pathological features in BrC patients. KEGG analysis has also shown that a variety of tRFs are involved in regulating the Wnt pathway and have been shown to play a role in a variety of diseases. For example, high expression of tRF-Gly-CCC-039 is associated with poor healing of diabetic foot, low expression of tsRNA-10277 is associated with high incidence of steroid-induced osteonecrosis of the femoral head (SONFH), high expression of tRF-22-8BWS7K092 is correlated with the severity of acute lung injury (ALI), and low expression of tsRNA-21109 is associated with the severity of systemic lupus erythematosus (SLE), and high expression of tRF-36-F900BY4D-84KRIME and tRF-23-87R8WP9IY, as well as low expression of tRF-40-86J8WPMN1E8Y7Z2R, were associated with high incidence of varicose vein (VV), and high expression of ts-34, was associated with high mortality of BrC. This article summarizes the biological function and mechanism of tRFs related to the Wnt pathway in cancer and other diseases, providing a new direction for subsequent translational medical research.

Gengnianchun (GNC) is a traditional remedy used for diminished ovarian reserve, but its underlying mechanisms remain unclear. This study aimed to explore these mechanisms in human granulosa-like cancer (KGN) cells pretreated with medicated rat serum (MRS) before H₂O₂ exposure. MRS pretreatment significantly alleviated H₂O₂-induced cell damage, including improvements in cell viability, superoxide dismutase and GSH-Px activities, and Bcl-2 expression. Conversely, H₂O₂ treatment increased apoptosis, autophagosomes, IL-1β, TNF-α, reactive oxygen species, malondialdehyde levels, and the expression of LC-II/LC3-I, Bax, and Beclin-1. GEO database analysis revealed significant differential expression of several miRNAs, including miR-548m. qPCR confirmed that MRS upregulated miR-548m expression, which was downregulated by H₂O₂ in a dose-dependent manner. Preincubation with MRS prevented the decline in miR-548m expression and mitigated H₂O₂-induced damage, including improvements in cell viability, apoptosis, autophagy, and oxidative stress. miR-548m suppressed FOXO3 3'-UTR luciferase activity, and anti-miR-548m enhanced it. Transfection with miR-548m reduced FOXO3 mRNA and protein levels, while anti-miR-548m increased them. These findings suggest that GNC protects against H₂O₂-induced ovarian damage by modulating the miR-548m/FOXO3 axis, triggering autophagy and apoptosis.

Supervillin (SVIL), the biggest member of the villin/gelsolin superfamily, has recently been reported to promote the metastasis of hepatocellular carcinoma by stimulating epithelial-mesenchymal transition (EMT). However, little is known about the roles of SVIL in the migration of colorectal cancer cells. Here, we investigated the effects of SVIL on the migration of cisplatin-resistant colorectal cancer cells. The model of cisplatin-resistant HCT116 cells (HCT116/DDP) was established. Migration was assessed after SVIL knockdown. Tumor metastasis was assessed using a mouse model with tail vein injection of colorectal cancer cells. The results showed that the expression of SVIL was upregulated in HCT116/DDP cells compared to that in their parental cells. Also, the HCT116/DDP cells showed increased cell migration and lung metastasis. Furthermore, we revealed that the expression of SVIL was associated with the migration of HCT116/DDP cells. Reduced SVIL expression inhibited migration and lung metastasis in HCT116/DDP cells. Further work showed that SVIL knockdown blocked cell migration by targeting zona occludens-1 (ZO-1) mediated tight-junction remodeling. The expression of ZO-1, but not occludin and cludin5, was downregulated after SVIL knockdown. Immunofluorescence indicated that the linear ZO-1 was interrupted while the SVIL knockdown reversed the interruption. This study displayed the relationship between SVIL and ZO-1 in cisplatin-resistant colon cancer cells, providing a new insight into the mechanism of colorectal cancer migration.

Cellular prion protein (PRNP) has been implicated in various physiological processes in different cell types, for decades. Little has been known how PRNP functions in multiple, yet related processes within a particular system. In our current study, with the aid of high-throughput RNA-sequencing technique, we have presented an overall transcriptome profile of rat vascular smooth muscle cells (VSMCs) with Prnp knockdown. Fifty-one genes were found to be differentially regulated, of which, genes involved in cell proliferation and endoplasmic reticulum (ER) stress pathway, show significant upregulation. That PRNP negatively regulates VSMC proliferation, has been demonstrated using immunoblot assays, BrdU incorporation assay and Ki-67 immunofluorescence staining. As revealed from our RNA-Seq data, ATF4, a downstream effector of the PERK arm of ER stress pathway is upregulated upon RNA interference of Prnp in VSMCs. As a result, the expression of the functional phosphorylated isoform of translation initiation factor eIF2α (p-eIF2α) is elevated. Additionally, we also showed that downregulation of Prnp leads to excess intracellular ROS accumulation, subsequently leading to splicing of Xbp1 mRNA and triggering unfolded protein response (UPR) within the cell. Therefore, our findings highlight that PRNP directly or indirectly modulates an array of biological processes and plays a pivotal role in preserving the equilibrium between excess proliferation and optimal endoplasmic reticulum function, in VSMCs.

MicroRNAs (miRNAs) have emerged as intricate players in rheumatoid arthritis (RA), holding promise as discerning biomarkers for diagnostic and prognostic purposes. The lack of sensitivity and specificity in current diagnostic techniques, such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), causes diagnosis delays in RA. The miR-146a and miR-155 act in inflammatory cascades and reduce joint deterioration, and miR-223 is paradoxical, acting differently in different illness scenarios. The microenvironment of RA is shaped by the complex modulation of gene expression and cytokine dynamics by miR-126 and miR-24. miRNAs serve as a promising candidate for precision medicine in the management of RA. There are obstacles encountered in validation, delivery optimization, and off-target effect mitigation before miRNA-based biomarkers may be applied in clinical settings. Machine learning (ML) and artificial intelligence (AI) have been used to integrate miRNA expression patterns with clinical data to greatly advance the treatment of RA. Because of the disease's inherent complexity and variability, these state-of-the-art models provide accurate predictions regarding the onset, development, and response to treatment of RA. By using clinical information and miRNA expression data, ML algorithms are revolutionizing the treatment of RA by predicting the onset and course of the disease with remarkably high accuracy. The development of therapeutic modalities and miRNA profiling has great potential to transform the diagnosis, prognosis, and treatment of RA, providing fresh hope for better patient outcomes.

Breast cancer ranks among the most prevalent cancers. Enhancing the effectiveness of chemotherapy and patient survival is the objective of many studies. In the literature, no study has investigated the combined effect of vitamin c and curcumin with chemotherapy drugs on cell viability in the MCF-7 cell line, nor the mechanism of inflammation induced by cancer drugs, both in vitro and in silico. Thus, the purpose of this study was to assess the synergistic effect of curcumin and vitamin c in combination with the chemotherapy drugs 5-fluorouracil and doxorubicin. The cytokine hub genes of the Toll-like receptor pathway for the administered drugs were identified using the Cytoscape program, and docking studies were conducted via the Cb Dock2 website. In silico analyses indicated that doxorubicin and curcumin displayed comparable characteristics, achieving the highest interaction scores (-10) with marker proteins, whereas 5-fluorouracil and vitamin c showed lower interaction scores. Cell viability was evaluated through MTT analysis and AO/PI staining, while the expression of inflammation-related markers IL-6, IL-10, and TNF-α proteins determined using the ELISA method. After 24 h, the cell viability of the chemotherapeutic drugs administered in combination with curcumin decreased by up to 28%. Subsequently, applications at 48 and 72 h were performed. These results indicate that the effect of curcumin on cell viability is significant when combined with chemotherapy drugs. In the ELISA test, a 52% expression of IL-6 was noted in MCF-7 cells treated with curcumin, whereas the IL-6 level decreased to 15% in the other experimental groups. An increase was observed in the TNF-α expression with 5-fluorouracil and doxorubicin compared to the control, while a notable decrease was recorded in the applications with vitamin c and curcumin (p < 0.05). This study demonstrates that vitamin c and curcumin exhibit a synergistic effect with chemotherapeutic agents in the inflammatory system.