The formation of human collagen requires the presence of Prolyl 3-hydroxylase 1 (P3H1), but the regulatory mechanism of P3H1 remained insufficiently understood. Our study aimed to identify the role of P3H1 in clear cell renal cell carcinoma (ccRCC). P3H1 expression in ccRCC was validated using multiple databases and in vitro experiments. We performed a correlation analysis of P3H1 with drug sensitivity, immune checkpoints, and immune cell infiltration using transcriptome and single-cell sequencing. Drawing upon the Encyclopedia of RNA Interactomes database, we selected P3H1 as the focal point of our investigation, meticulously uncovering the intricate network of microRNAs and lncRNAs that potentially orchestrate ceRNA mechanisms. This study employs a multidimensional approach integrating vitro assays and multi-omics bioinformatics analyses to investigate P3H1's impact on ccRCC prognosis, immune modulation, immune checkpoints, ceRNA regulatory network, drug sensitivity, and therapeutic responses, aiming to uncover new insights into its therapeutic potential and inform future clinical strategies.
IntroductionLung cancer as the most common cancer in the world represents a major public health problem (1).Worldwide it has the highest rate of cancer mortality, exceeding the mortality rates of colorectal, breast and prostate cancers combined (2).Despite major advances in the treatment and management of lung cancer, most patients with lung cancer eventually die of this disease.Because conventional therapies have failed to make a major impact on survival, newer approaches are necessary in the battle against lung cancer.The poor lung cancer survival figures argue powerfully for new approaches to control this disease through chemoprevention, which has been defined as the use of agents that could reverse, suppress or completely halt tumor development.Developing novel mechanism-based chemopreventive approaches for lung cancer which humans can accept has become an important goal.Many traditional Chinese medicine (TCM) formulas have been used in cancer therapy.JIN formula, an ancient herbal formula from classical book JIN KUI YAO LUE (Golden Chamber) for the treatment of lung cancer, which is composed of Ophiopogon japonicus 30g, Prepared Rhizoma Pinelliae15g, Ginseng radix 30g, Glycyrrhiza radix 12g, Peach Kernel 15g, Unprepared Coix lachryma jobi seed 30g, Chinese waxgourd seed 30g, and Phragmititis Caulis 30g.TCM theory regarded that lung cancer is related with both deficiency of Qi and Yin, or Qi insufficiency of the Spleen and Lung, as well as pathological changes of Qi stagnation, blood stasis, and accumulation of phlegm and toxin.Whereas, JIN formula could replenish both Qi and Yin, strengthen the Spleen and Lung, clear lung, resolve phlegm, activate blood circulation and remove stasis.
The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q, SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional regulation genes during the stage of tumor initiation and invasion. Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network of colorectal cancer metastasis related gene NGX6 have been thoroughly elucidated. These fruitful Results imply that the changes of key molecules in crucial signal pathway will cause severe dysfunction in signal transduction and gene regulation network in polygenic tumors, indicating that in the category of pathogenesis,these tumors may further classify as the "Disease of gene signal transduction and gene regulation network disorder". The researches have laid solid foundation for revealing the molecular mechanism and transcriptomic regulation of polygenic tumors at different stages.
Succinate dehydrogenases (SDH), including SDHA, SDHB, SDHC, and SDHD, form the respiratory complex II in the mitochondria and play an important role in cell growth and homeostasis. In order to evaluate the expression and functional significance of SDH in colorectal cancer, the expression of four SDH subunits was analyzed, and SDHB protein was found to be significantly lower in colorectal cancer tissues. In vitro experiments including cell growth assay, colony formation assay, cell cycle analysis, and nude mouse xenograft of SDHB-transfected colorectal cancer cell line SW620 were performed. Notably, reduced SDHB expression in tumor tissues was associated with tumor de-differentiation, and restoration of SDHB could inhibit the growth of cancer cells both in vitro and in vivo. Furthermore, cDNA microarray of SDHB-transfected cell line showed that most of the differentially expressed genes are related to cell cycle control and cell proliferation. Thus, we conclude that SDHB expression is significantly decreased in human colorectal cancer tissues, and reconstitution of SDHB in colorectal cancer may be a potential therapeutic approach to inhibit aggressiveness of colorectal cancer.
Lung cancer is the most common cancer worldwide and the leading cause of cancer-related mortality. Despite significant advances towards understanding its causal mechanisms, the morbidity and mortality rates of lung cancer remain high, due to cancer recurrence and metastasis (1).
﨩bjective: [WT5BZ]Our aims were to study the prim ar y culture of rat peritoneal mesothelial cell (PMC) and to evaluate the expressio n of hexokinase (HK) activity. [WT5HZ]Methods: [WT5BZ]We obtained the PMC by using enzymatic disaggregation. Standard G6PDH coupled assay was used to measu re the total activity of HK. [WT5HZ]Results: [WT5BZ]It was approximately 5 to 8 days to reach confluency for primary and passaged cells. The basic activity of HK in PMC of rat was (4.80±0.39) U/g protein. [WT5HZ]Conclusion: [WT5BZ ]Trypsin EDTA treatment is a reproducible technique for the primary culture of peritoneal mesothelial cell. The expression of HK in PMC suggested that HK take part in the regulation of the glucose metabolism duing peritoneal dialysis and h ave a great effect on peritoneal dialysis ultrafilatration.
The aim of the present study was to elucidate the underlying mechanism of antitumor activity of gambogic acid (GA) in colon cancer. Human colon cancer SW620 cells were divided into five treatment groups, including no-treatment control (NC), low dose GA (10 µg/ml), medium dose GA (50 µg/ml), high dose GA (100 µg/ml) and 5-fluorouracil (10 µg/ml). Differences in cell proliferation, apoptosis and cell cycle, invasion, and migration were measured between groups using MTT, flow cytometry, transwell and wound-healing assays, respectively. Western blotting was used to analyze relative protein expression levels of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), P21, and matrix metalloprotease (MMP)-2 and -9 between groups. Compared with the NC group, GA (low, middle and high) inhibited SW620 cell proliferation, invasion and migration (all P<0.05). Furthermore, there were significant differences in proliferation, invasion and migration between groups administered with different doses of GA (all P<0.05). Compared with the NC group, the expression levels of PI3K, AKT, phosphorylated-AKT, P21 and MMP-2 and -9 were significantly altered in a dose dependent manner following treatment with GA (all P<0.05). The results of the current study indicated that GA suppressed proliferation and dispersion of human colon cancer cells in a dose-dependent manner, possibly through a PI3K/AKT/P21/MMP-2/9-dependent pathway.
The mammalian STE20-like protein kinase 1 (MST1)-MOB kinase activator 1 (MOB1) complex has been shown to suppress the oncogenic activity of Yes-associated protein (YAP) in the mammalian Hippo pathway, which is involved in the development of multiple tumors, including pancreatic cancer (PC). However, it remains unclear whether other MST-MOB complexes are also involved in regulating Hippo-YAP signaling and have potential roles in PC. Here, we report that mammalian STE20-like kinase 4 (MST4), a distantly related ortholog of the MST1 kinase, forms a complex with MOB4 in a phosphorylation-dependent manner. We found that the overall structure of the MST4-MOB4 complex resembles that of the MST1-MOB1 complex, even though the two complexes exhibited opposite biological functions in PC. In contrast to the tumor-suppressor effect of the MST1-MOB1 complex, the MST4-MOB4 complex promoted growth and migration of PANC-1 cells. Moreover, expression levels of MST4 and MOB4 were elevated in PC and were positively correlated with each other, whereas MST1 expression was down-regulated. Because of divergent evolution of key interface residues, MST4 and MOB4 could disrupt assembly of the MST1-MOB1 complex through alternative pairing and thereby increased YAP activity. Collectively, these findings identify the MST4-MOB4 complex as a noncanonical regulator of the Hippo-YAP pathway with an oncogenic role in PC. Our findings highlight that although MST-MOB complexes display some structural conservation, they functionally diverged during their evolution.
Ehm2 [also known as erythrocyte membrane protein band 4.1‑like protein 4B (EPB41L4B)] is a member of the NF2/ERM/4.1 superfamily. The overexpression of Ehm2 has been observed in metastatic cancer cells. Through alternative splicing, the Ehm2 gene produces two transcript variants that encode the two different isoforms, Ehm2/1 and Ehm2/2. The biological functions of these different Ehm2 transcript variants remain unclear. The present study aimed to determine the expression of the Ehm2 variants in lung adenocarcinoma and their involvement in the disease progression of the patients. The expression of Ehm2 transcript variants in human lung adenocarcinoma tissues was analyzed using immunohistochemistry and western blot analysis. Ehm2 variants were overexpressed or knocked down in A549 human lung adenocarcinoma cells. The consequent effects of the genetic modifications on the cellular functions of lung cancer cells were then examined using in vitro cell viability, invasion and migration assays. The expression of epithelial‑mesenchymal transition (EMT)‑related markers was evaluated by western blot analysis in the cell models. The association of Ehm2 variant expression with patient survival was analyzed using Kaplan‑Meier survival analysis. The expression of Ehm2/1 was significantly decreased in lung cancers compared with the paired normal lung tissues (P<0.05), while the Ehm2/2 protein levels were higher in the tumors than in the paired normal lung tissues, although this was not statistically significant. The overexpression of Ehm2/1 exerted inhibitory effects, while the knockdown of Ehm2/1 promoted the growth, invasion and migration of A549 cells in vitro. Ehm2/2 was expressed at low levels in the A549 cells and the enforced expression of Ehm2/2 significantly increased the invasiveness and migration of the A549 cells. Immunofluorescence staining revealed that Ehm2/1 was confined to the plasma membrane, while Ehm2/2 was observed at both the plasma membrane and cytoplasm. The overexpression of Ehm2/1 resulted in the upregulation of the epithelial marker, E‑cadherin, and in the decreased expression of the mesenchymal markers, N‑cadherin and Snail1, while the knockdown of Ehm2/1 and the enforced expression of Ehm2/2 had the opposite effects on the protein levels of EMT‑related markers. Kaplan‑Meier survival analysis revealed that higher Ehm2/1 transcript levels were associated with the longer survival of patients with lung adenocarcinoma, while the lower expression of Ehm2/2 exhibited a similar association with patient survival. Taken together, the two Ehm2 variants appear to be differentially expressed in lung adenocarcinoma. Ehm2/1 may function as a putative tumor suppressor in the disease progression of lung adenocarcinoma, while Ehm2/2 may have an opposite function.
Objective:To study the expression of extracellular matrix metalloproteinase inducer(EMMPRIN/CD147) in human laryngeal squamous cell carcinoma and the relationship between the expressions and the clinical features.Method:The expressions of EMMPRIN were detected by the method of immunohistochemical SP in 42 specimens taken from the patients with laryngeal squamous cell carcinoma, 28 specimens from precancerous lension and 20 specimens from normal laryngeal tissues.Result:Positive expressions rates of EMMPRIN in the specimens from laryngeal squamous cell carcinoma, precancerous lension and normal laryngeal tissues were 88.1%, 57.1% and 5.0%, the intensive expressions rates were 52.4%, 10.7% and 0%. There were significant differences among laryngeal squamous cell carcinoma,precancerous lension and normal laryngeal tissues. In laryngeal squamous cell carcinoma, the expressions of EMMPRIN had a significant relevance to clinical phases and lymph node matastasis. The intense expsessions rate in phase Ⅲ-Ⅳ was much higher than that in phase Ⅰ-Ⅱ, while the intense expressions rate in cases with lymph node matastasis was higher than in those cases without lymph node matastasis.Conclusion:The expression of EMMPRIN has relationship with the pathological type of laryngeal tumor and has relevance to clinical stage and lymph node matastasis of laryngeal carcinoma.
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