Nan Liu's research while affiliated with China Academy of Traditional Chinese Medicine and other places

Background Non‐small cell lung cancer (NSCLC) is a highly malignant tumor with limited effective treatment options. This study aimed to investigate the regulatory mechanism of Glabrene on NSCLC through its interaction with FGFR3. Methods HCC827 cells were implanted into nude mice and treated with Glabrene. Tumor volume was monitored at 0, 3, 6, and 9 days after medical treatment. Tissue analysis included Hematoxylin and Eosin (HE) and Terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP Nick End Labeling (TUNEL) staining, as well as immunohistochemistry for Ki67, ERK1/2, and p‐ERK1/2 expression. Cell viability was determined with the CCK8 method. We utilized immunofluorescence techniques to observe apoptosis, as well as the levels of E‐cadherin and Vimentin expression. Cellular proliferation was determined via plate cloning assay and cellular mobility was determined via scratch assay. Cellular invasion ability was assessed via a transwell assay. mRNA and protein levels of FGFR3, MMP1, MMP9, vimentin, E‐cadherin, ERK1/2, and p‐ERK1/2 were detected via qPCR and Western blot. IGF‐1, VEGF, and Estradiol (E2) levels were measured through Enzyme linked immunosorbent assay (ELISA). Results This study verified that Glabrene was capable of suppressing tumor growth in NSCLC mice, reversing tumor tissue's pathological morphology, attenuating the capacities of cancerous cells' proliferation, migration, and invasion, and leading to apoptosis. Besides, Glabrene could reduce the FGFR3 expression in HCC827 cells. Over‐expression of FGFR3 promotes the proliferation of HCC827 cells, increase both contents of IGF‐1, VEGF, and E2, and expressions of MMP1, MMP9, vimentin, and p‐ERK1/2, while Glabrene inhibited FGFR3. Glabrene, and inhibition of FGFR3 expression were capable of decreasing FGFR3, MMP1, MMP9, vimentin, and p‐ERK1/2 expression, as well as contents of IGF‐1, VEGF, and E2 in model mice and HCC827 cells, and promoting the expression of E‐cadherin. Conclusion Glabrene has the potential as a therapeutic agent for NSCLC by reducing cancer invasion and migration through the inhibition of ERK1/2 phosphorylation and suppression of epithelial‐mesenchymal transition (EMT).

Background: Breast cancer (BC) is the most common malignant tumor in women. Aim: To investigate BC-associated hub genes to obtain a better understanding of BC tumorigenesis. Methods: In total, 1203 BC samples were downloaded from The Cancer Genome Atlas database, which included 113 normal samples and 1090 tumor samples. The limma package of R software was used to analyze the differentially expressed genes (DEGs) in tumor tissues compared with normal tissues. The cluster Profiler package was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of upregulated and downregulated genes. Univariate Cox regression was conducted to explore the DEGs with statistical significance. Protein-protein interaction (PPI) network analysis was employed to investigate the hub genes using the CytoHubba plug-in of Cytoscape software. Survival analyses of the hub genes were carried out using the Kaplan-Meier method. The expression level of these hub genes was validated in the Gene Expression Profiling Interactive Analysis database and Human Protein Atlas database. Results: A total of 1317 DEGs (fold change > 2; P < 0.01) were confirmed through bioinformatics analysis, which included 744 upregulated and 573 downregulated genes in BC samples. KEGG enrichment analysis indicated that the upregulated genes were mainly enriched in the cytokine-cytokine receptor interaction, cell cycle, and the p53 signaling pathway (P < 0.01); and the downregulated genes were mainly enriched in the cytokine-cytokine receptor interaction, peroxisome proliferator-activated receptor signaling pathway, and AMP-activated protein kinase signaling pathway (P < 0.01). Conclusion: In view of the results of PPI analysis, which were verified by survival and expression analyses, we conclude that MAD2L1, PLK1, SAA1, CCNB1, SHCBP1, KIF4A, ANLN, and ERCC6L may act as biomarkers for the diagnosis and prognosis in BC patients.

The present study investigates the underlying mechanisms of treatment with osthole (OST) combined with lobaplatin in human triple-negative MDA-MB-231 breast cancer cells. Human triple-negative MDA-MB-231 breast cancer cells were treated with different concentrations of OST (0.1, 1, 5, 10, 20, 50, and 100 μM) alone or in combination with 10 μM lobaplatin for 48 h. Cell viability was determined and compared between the treatment groups with the Cell Counting Kit-8 assay. Transcriptome sequencing (Project Number: M-GSGC0250521) was employed to elucidate the gene expression profile of the control group and the OST treatment group, and differentially expressed genes (DEGs) were identified based on the following criteria: log2FC > 0, P < 0.05. KEGG enrichment analysis was employed to determine the biological functions of these DEGs and the related signaling pathways. Finally, flow cytometry and western blotting were used to assess differences in the apoptosis rate and protein expression in MDA-MB-231 cells subjected to different treatments. The findings showed that OST inhibited the growth of MDA-MB-231 cells in a concentration-dependent manner and cell proliferation was significantly inhibited (as indicated by a decrease of 40%) at the OST concentration of 50 μM (P < 0.05). Transcriptome sequencing identified 4712 DEGs, including 2169 upregulated DEGs and 2543 downregulated DEGs. Enrichment analysis indicated that the DEGs played a role in apoptosis, p53 signaling, DNA replication, and cell cycle. In vitro experiments showed that OST and lobaplatin could significantly induce apoptosis in the MDA-MB-231 cells (P < 0.05), as indicated by elevation in the translation level of p53/Bax/caspase-3 p17 and downregulation of the Bcl-2 protein. Finally, combined treatment with OST and lobaplatin had an enhanced anti-tumor effect (P < 0.05) on proliferation and apoptosis, as well as more obvious effects on the related proteins (p53, Bax, Bcl-2, and caspase-3 p17). Thus, OST enhanced the apoptosis-mediated growth inhibitory effect of lobaplatin on breast cancer cells and has potential for the treatment of breast cancer in the future.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes poor outcome. Dysregulation of long noncoding RNA (lncRNA) is involved in HCC. Upregulation of the lncRNA PCNAP1 has been reported to promote HBV-infectious HCC growth, but its clinical significance and underlying mechanisms in HCC development remain unclear. Here, we report that PCNAP1 expression is increased in both HBV-infectious and noninfectious HCC tissues compared with matched normal tissues, and its upregulation correlates with poor survival rates of HCC patients. Furthermore, we found that PCNAP1 promotes HCC cell proliferation through acting as a competitive endogenous RNA (ceRNA) to sponge miR-340-5p, which has been reported to directly inhibit ATF7 expression in HCC cells. Moreover, the PCNAP1/miR-340-5p/ATF7 signaling associates with the poor survival rates of HCC patients. Collectively, our findings suggest that the PCNAP1/miR-340-5p/ATF7 signaling may be a potential biomarker for the prognosis of HCC patients and a potential therapeutic target for HCC.