Epithelial-Mesenchymal Transformation Promotes the Progression of Hepatocellular Carcinoma through NF-κB/MMP9 Axis.

BACKGROUND: Primary liver cancer (PHC) stands as one of the most prevalent malignant diseases in clinical settings. Studies have indicated that transcatheter arterial chemoembolization (TACE) treatment exhibits superior clinical outcomes, potentially increasing the complete necrosis rate in patients with PHC. A correlation exists between the clinical outcomes of TACE surgery and the process of epithelial-mesenchymal transition (EMT), yet the underlying mechanism remains a mystery. Hence, it is crucial to investigate the impact and mechanism of EMT on hepatocellular carcinoma (HCC). METHODS: Retrospectively, patients with advanced liver cancer who underwent TACE were selected and categorized into two groups based on the assessment of clinical efficacy: the effective group and the ineffective group. The expression levels of nuclear factor-kappa B (NF-κB), matrix metalloproteinase 9 (MMP9), Ki-67, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), Vimentin, E-cadherin, and N-cadherin in tumor tissues were evaluated using reverse transcription-polymerase chain reaction (RT-PCR). In vitro, Huh7 cells were cultured, and lentivirus infections were utilized to inhibit the overexpression of NF-κB and MMP9. The determination of EMT and cell viability was conducted through Cell Counting Kit-8 (CCK-8) assays, RT-PCR, and Western blot. RESULTS: Sixty patients diagnosed with advanced liver cancer were selected for the study. Based on their clinical outcomes, 30 patients with advanced hepatocellular carcinoma were categorized into the effective group, while the remaining 30 patients were categorized into the ineffective group. The results of the Western blot analysis indicated that, in comparison to the effective group, the expression levels of NF-κB, MMP9, Ki-67, Bcl-2, Vimentin, and N-cadherin were significantly higher in the tumor tissues of the ineffective group. Conversely, the expression of Bax and E-cadherin was notably lower in the effective group. Following the individual knockdown of NF-κB and MMP9, the cell experiments revealed a remarkable decrease in the expression levels of Ki-67, Bcl-2, Vimentin, and N-cadherin, whereas the expression of Bax and E-cadherin showed significant elevation (p < 0.05). Furthermore, there was a significant increase in cell viability and a decrease in cell apoptosis after the knockdown of NF-κB and MMP9. CONCLUSIONS: The NF-κB/MMP9 signaling axis serves as a pivotal regulator that fosters proliferation and impedes apoptosis in Huh7 cells by modulating the process of EMT.

BMSCs attenuate radiation-induced brain injury induced hippocampal neuronal apoptosis through a PI3K/Akt/Bax/Bcl-2 signaling pathway.

BACKGROUND: Bone marrow mesenchymal stem cell (BMSCs) -based therapies represent a promising treatment for neurological disorders. However, therapeutic effects and mechanisms of BMSCs transplantation for radiation-induced brain injury (RIBI) have not been fully disclosed. In this article, we explored the functions of BMSCs transplantation on RIBI and investigated the protective effects of BMSCS on hippocampal neurons in RIBI as well as the related molecular mechanisms. MATERIALS AND METHODS: 6-8 weeks-old rats were used to build a RIBI model. Rats in BMSC group were treated with a 3 × 106 BMSCs injection through the tail vein on the 1st day and 8th day after irradiation; rats in both control and RIBI groups were injected with an equivalent volume of physiological saline for comparisons. The Morris water maze was applied to detect the variations in cognitive function after RIBI. MRS was performed to test changes in NAA/Cr, indicating neuronal apoptosis after RIBI. TUNEL was conducted to detect apoptosis of rat hippocampal neurons, and HE staining was carried out to show pathological variations in the hippocampal region of rats. Protein levels of PI3K, P-PI3K, AKT, P-AKT, Bcl-2, and Bax proteins of rats in the hippocampal area were all determined by Western blot. RESULTS: Cognitive function was reduced and hippocampal neurons underwent apoptosis in the rats of the RIBI group, and cognitive abilities, histopathological alterations, and apoptosis of hippocampal neurons were significantly improved after BMSCs treatment; the expression of PI3K, P-PI3K, AKT, P-AKT, and Bcl-2 proteins, in the hippocampal region of the rat, was up-regulated, and Bax proteins were down-regulated. CONCLUSIONS: BMCSs can inhibit hippocampal neuronal apoptosis in RIBI, and the mechanism may be associated with the up-regulation of Bcl-2 and down-regulation of Bax by the PI3K/AKT signaling pathway.

miR-26b Targets CEP135 Gene to Regulate Nasopharyngeal Carcinoma Proliferation and Migration by NF-κB Pathway.

To screen microRNAs (miRNAs) and analyze their role in the nasopharyngeal carcinoma (NPC) development through differential analysis and cytological validation of the nasopharyngeal carcinoma dataset. The Gene Expression Omnibus (GEO) database of NPC-related data were utilized to screen for differential miRNAs, downstream target genes and relevant pathways, and the relationships among them were verified by luciferase reporter assay and cell co-culture. To analyze the function of miRNAs and downstream target genes, a series of mimics, inhibitors or Small interfering RNAs (siRNAs) targeting the downstream target genes were transfected into NPC cells or normal epithelial cells by cell transfection techniques. Cell Counting Kit-8 (CCK8), Transwell, Enzyme-linked immunosorbent assay (ELISA) apoptosis, and western blotting were adopted to determine the changes in cell activity, invasiveness, and apoptosis after differential miRNA and target gene overexpression or downregulation. Differential analysis of miRNA dataset showed that the expression of miR-26b was significantly downregulated in NPC, in agreement with the validation results of nasopharyngeal carcinoma cell lines. And downregulation of miR-26b expression in normal nasopharyngeal epithelial cells transformed the cells to tumors. CEP135 was identified as the miR-26b downstream target gene by mRNA dataset analysis, and a luciferase reporter test revealed a direct targeting link between the two. Upregulation of CEP135 levels in nasopharyngeal cancer cell lines increased cell activity, accelerated cell migration, and inhibited apoptosis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that CEP135 exerted the above effects on cells via the NF-κB pathway, and co-culture with NF-κB pathway blockers reversed cell biological behavior to the level of the control group. MiR-26b downregulation leads to CEP135 overexpression and NF-κB pathway activation in NPC, which enhances proliferation, migration, and prevents apoptosis of nasopharyngeal carcinoma cells. Therefore, the study further clarifies the biological behavior mechanism of NPC and suggests new therapeutic options for NPC.

LncRNA OXCT1-AS1 promotes the proliferation of non-small cell lung cancer cells by targeting the miR-195/CCNE1 axis.

Background: Long non-coding RNAs (lncRNAs) are involved in various biological processes in non-small cell lung cancer (NSCLC). This study aimed to investigate the key lncRNA OXCT1-AS1/miR-195/CCNE1 axis in the development of NSCLC and its potential molecular mechanism. Methods: LncRNA OXCT1-AS1 is considered to be a competitive endogenous RNA (ceRNA) and its potential targeting microRNAs (miRNAs) were predicted through LncBase predicted v.2. The expression of OXCT1-AS1 and miR-195 in NSCLC tissues and cells was detected by reverse transcription polymerase chain reaction (RT-PCR). The Cell Counting Kit-8 (CCK-8) and cell colony-forming test were used to detect the effect of cell proliferation. RT-PCR was used to detect the expression changes of CCND1 and CCNE1. Western Blot was used to detect the changes of the CCNE1 cell cycle protein. Dual luciferase activity was used to determine the potential mechanism of lncRNA OXCT1-AS1. Results: LncRNA OXCT1-AS1 was highly expressed and miR-195 was lowly expressed in NSCLC tissues and cell lines. LncBase predicted v.2.0 reported a high-scoring binding between OXCT1-AS1 and miR-195. The luciferase reporter assay defined the regulatory relationship between OXTC1-AS1 and miR-195. In NSCLC cells, knockdown of OXCT1-AS1 significantly increased the expression of miR-195, decreased the proliferation and colony formation number of cancer cells, and reduced the expression of CCND1 and CCNE1. Meanwhile, overexpression of miR-195 significantly inhibited the cell proliferation and colony formation number, and reduced the expression of CCND1 and CCNE1. Furthermore, according to the results of the dual-luciferase activity assay, miR-195 targeted the 3' untranslated regions (3' UTRs) of CCNE1, validating that CCNE1 is a direct target of miR-195. Overexpression of CCNE1 restored the role of OXCR1-AS1 in NSCLC cells. Conclusions: LncRNA OXCT1-AS1 can regulate the proliferation of NSCLC cells via miR-195/CCNE1 signaling. Therefore, OXCT1-AS1 may act as a prospective biomarker and therapeutic target for patients with NSCLC.

Nursing Observation on the Clinical Efficacy and Toxicity of Lobaplatin Compared with Cisplatin in the Treatment of Locally Advanced Hypopharyngeal Carcinoma Based on Intelligent CT Imaging.

With the acceleration of people's life rhythm, the incidence of hypopharyngeal cancer has generally increased. This study mainly explores the clinical efficacy and toxicity of lobaplatin compared with cisplatin in the treatment of locally advanced hypopharyngeal carcinoma based on intelligent CT imaging. Group A received lobaplatin combined with docetaxel induction chemotherapy for 2 cycles after cisplatin combined with intensity-modulated radiotherapy. Lobaplatin was added to the patient, then, 200 ml of 5% glucose was added, and the patient was injected intravenously for 1.8 hours. After 2 cycles of induction chemotherapy, simultaneous lobaplatin chemotherapy was performed every week for 5 weeks (10 mg/week), and the efficacy was evaluated after 4 consecutive courses of treatment. Group B received cisplatin combined with docetaxel induction chemotherapy after 2 cycles of cisplatin combined with intensity-modulated radiotherapy. Group C was the control group and was not treated with cisplatin or docetaxel. Stomach protection treatment was given in time throughout the treatment process. All patients underwent normal CT (NCCT) and enhanced CT (CECT) examinations before treatment. We extracted 5 mm plain scan CTQNCCT and enhanced CT (CECT) digital DICOM images from the PACS system for omics feature selection. Toxic and side effects are rated in different degrees according to the evaluation criteria of the National Cancer Institute (NCD) common adverse events. Blood routine and liver and kidney function tests were checked every week, and the medication was stopped immediately if there is a serious reaction. In addition, in vitro cell culture was set up to test the inhibitory effect of cisplatin and lobaplatin on the proliferation of cancer cells. The incidence of digestive tract reaction was 13.0% in the A plan group and 58.3% in the B plan group. The A group was lower than the B group, and the difference was statistically significant (P=0.001 < 0.05). Compared with cisplatin, lobaplatin has a milder gastrointestinal reaction, and there is no common hepatic and renal toxicity of cisplatin. This study is helpful to provide guidance for the clinical efficacy of locally advanced hypopharyngeal cancer treatment.