sincalide and Cell-Transformation--Neoplastic

Gastric cancer is one of the most common and deadly cancers worldwide. Basic leucine zipper transcription factor ATF-like 3 (BATF3) plays a key role in tumor immunity. However, the function of BATF3 in gastric cancer remains unclear. Here, we demonstrated BATF3 positively regulated proliferation and radioresistance of gastric cancer cells by regulating S1PR1/STAT3 pathway.. The RNA-seq analyzed the gene expression by UALCAN web portal and Tumor Immune Estimation Resource. RT-qPCR and western blot was performed to verify BATF3 expression in gastric cancer cells. The assays of CCK-8, EdU incorporation and colony formation were used to analyze cell proliferation, and radioresistance in AGS and MKN45 cells. Flow cytometry was used to detect the cell apoptosis of AGS and MKN45 in treatment with si-BATF3 or radiation. Finally, western blot was performed to measure the expression of cell apoptosis-related modules including Bax, cleaved-caspase3, cleaved-PARP and assess the regulation of S1PR1/STAT3 pathway.. BATF3 expression was upregulated in gastric cancer cells. Knockdown of BATF3 suppressed proliferation, radioresistance but promoted the radiation-induced apoptosis of gastric cancer cells through positively regulating S1PR1 expression and STAT3 phosphorylation.. Knockdown of BATF3 inhibits gastric cancer cell growth and radioresistance via S1PR1/STAT3 pathway. BATF3 would become a potential diagnostic indicator for gastric cancer and target of therapeutic treatment.

Topics: Apoptosis; Basic-Leucine Zipper Transcription Factors; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Humans; Poly(ADP-ribose) Polymerase Inhibitors; Signal Transduction; Sincalide; Sphingosine-1-Phosphate Receptors; STAT3 Transcription Factor; Stomach Neoplasms

LINC01140 has been known to be involved in various cancers. However, its underlying molecular mechanism in breast cancer (BC) needs further exploration.. The LINC01140, miR-452-5p, and RGS2 levels in BC cells and tissues were evaluated by means of RT-qPCR and western blotting. The variations in the biological functions of BC cells were analyzed through CCK-8, transwell, western blotting, and xenograft experiments to observe cell viability, migration, levels of apoptosis-related proteins (Bax and Bcl-2), and tumor growth. The correlations existing among LINC01140, miR-452-5p, and RGS2 were validated through luciferase reporter and RIP assays.. LINC01140 and RGS2 were remarkably downregulated in BC cells and tissues, whereas miR-452-5p was upregulated. LINC01140 overexpression diminished BC cell viability, migration, and tumor growth and facilitated apoptosis. MiR-452-5p upregulation enhanced cell viability and migration and suppressed apoptosis. Nevertheless, the additional upregulation of LINC01140 could reverse the promotive effects of miR-452-5p upregulation. Additionally, RGS2 overexpression inhibited the malignant phenotypes of BC cells, but miR-452-5p upregulation abolished this effect. In terms of mechanisms, LINC01140 acted as a miR-452-5p sponge. Moreover, RGS2 was determined to be miR-452-5p's downstream target gene in BC.. LINC01140 functioned as an antitumor agent in BC by sponging miR-452-5p to release RGS2. This hints that LINC01140 is a promising therapeutic target for BC.

Topics: Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Breast Neoplasms; Carcinogenesis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Female; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; RGS Proteins; Sincalide

Ultrasound-targeted microbubble destruction (UTMD) is a novel adjuvant tumor therapeutic method by enhancing exogenous gene transfection to target tissues. This study aims to investigate the role of microRNA-492 (miR-492) in non-small cell lung cancer (NSCLC) and further analyze the effects of UTMD-mediated miR-492 inhibitor on tumorigenesis.. The expression of miR-492 was detected by qRT-PCR. Co-transfection of microbubbles and miR-492 inhibitor with Lipofectamine 3000 was performed to achieve UTMD-mediated miR-492 inhibition in NSCLC cells. CCK-8 and Transwell assay were used to determine NSCLC cell proliferation, and the migration and invasion.. High expression of miR-492 was associated with poor prognosis in NSCLC patients. miR-492 inhibitor suppressed tumor cell proliferation, migration and invasion, and UTMD not only increased the transfection efficiency of miR-492 inhibitor, but also enhance the inhibitory effects on cell biological behaviors.. The results showed that the expression level of miR-492 was up-regulated in NSCLC tissue samples and cells. Silencing of miR-492 inhibited NSCLC cell proliferation, migration and invasion, and UTMD-mediated miR-492 inhibitor could promote more significant inhibition, which indicated that UTMD-mediated miR-492 inhibitor might provide a novel strategy for the treatment of NSCLC.KEY MESSAGESmiR-492 inhibitor inhibited cell proliferation, migration and invasion.UTMD-mediated miR-492 inhibitor can promote more significant inhibition.UTMD-mediated miR-492 inhibitor provide a new strategy for NSCLC.

Topics: Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Cell Proliferation; Cell Transformation, Neoplastic; Female; Gene Expression; Humans; Lipids; Lung Neoplasms; Male; Microbubbles; MicroRNAs; Middle Aged; Real-Time Polymerase Chain Reaction; Sincalide; Transfection; Treatment Outcome; Ultrasonics; Ultrasonography

Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene whose reduced expression may play an important role in the development and progression of esophageal squamous cell cancer (ESCC). The aim of this study was to investigate the clinical relevance of RUNX3 in ESCC patients and effects of overexpression on biological behaviour of Eca109 cells in vitro and in vivo. Immunohistochemistry was performed to detect the clinical relevance of RUNX3 and lymph node metastasis in 80 ESCC tissues and 40 non-cancerous tissues using the SP method. RT-PCR and Western blotting were applied to assess the RUNX3 level and verify the Eca109 cell line with stable overexpression. Localization of RUNX3 proteins was performed by cell immunofluorescence. CCK-8 and Scrape motility assays were used to determine proliferation and migration and the TUNEL assay to analyze cell apoptosis. Invasive potential was assessed in cell transwell invasion experiments. In nude mice, tumorigenesis in vivo was determined. Results showed decreased expression of RUNX3 in esophageal tissue to be significantly related to lymph node metastasis (LNM) (P<0.01). In addition, construction of a recombinant lentiviral vector and transfection into the human ESCC cell line Eca109 demonstrated that overexpression could inhibit cell proliferation, migration and invasion, and induce apoptosis. The in vivo experiments in mice showed tumorigenicity and invasiveness to be significantly reduced. Taken together, our studies indicate that underexpression of RUNX3 in human ESCC tissue is significantly correlated with progression. Restoration of RUNX3 expression significantly inhibits ESCC cells proliferation, migration, invasion and tumorigenesis.

Topics: Animals; Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Core Binding Factor Alpha 3 Subunit; Disease Progression; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Lymphatic Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; RNA, Messenger; Sincalide; Tumor Suppressor Proteins

Genetic mutations that give rise to active mutant forms of Ras are oncogenic and found in several types of tumor. However, such mutations are not clear biomarkers for disease, since they are frequently detected in healthy individuals. Instead, it has become clear that elevated levels of Ras activity are critical for Ras-induced tumorigenesis. However, the mechanisms underlying the production of pathological levels of Ras activity are unclear. Here, we show that in the presence of oncogenic Ras, inflammatory stimuli initiate a positive feedback loop involving NF-κB that further amplifies Ras activity to pathological levels. Stimulation of Ras signaling by typical inflammatory stimuli was transient and had no long-term sequelae in wild-type mice. In contrast, these stimuli generated prolonged Ras signaling and led to chronic inflammation and precancerous pancreatic lesions (PanINs) in mice expressing physiological levels of oncogenic K-Ras. These effects of inflammatory stimuli were disrupted by deletion of inhibitor of NF-κB kinase 2 (IKK2) or inhibition of Cox-2. Likewise, expression of active IKK2 or Cox-2 or treatment with LPS generated chronic inflammation and PanINs only in mice expressing oncogenic K-Ras. The data support the hypothesis that in the presence of oncogenic Ras, inflammatory stimuli trigger an NF-κB-mediated positive feedback mechanism involving Cox-2 that amplifies Ras activity to pathological levels. Because a large proportion of the adult human population possesses Ras mutations in tissues including colon, pancreas, and lung, disruption of this positive feedback loop may be an important strategy for cancer prevention.

Topics: Animals; Carcinoma, Pancreatic Ductal; Cell Transformation, Neoplastic; Ceruletide; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Enzyme Induction; Esters; Feedback, Physiological; Gabexate; Gene Expression Regulation, Neoplastic; Gene Knock-In Techniques; Genes, ras; Guanidines; Humans; I-kappa B Kinase; Inflammation; Inflammation Mediators; Lipopolysaccharides; Mice; Mice, Transgenic; Neoplasm Proteins; NF-kappa B; Pancreas; Pancreatic Neoplasms; Pancreatitis, Chronic; Precancerous Conditions; Proto-Oncogene Proteins p21(ras); Sincalide

Cholecystokinin (CCK-A) and gastrin (CCK-B) receptors have been demonstrated in the azaserine-induced rat pancreatic carcinoma DSL-6. In order to determine at what stage in azaserine-induced pancreatic carcinogenesis gastrin (CCK-B) receptors are first expressed, we examined the binding of [125I]gastrin-I to normal rat pancreas, azaserine-induced premalignant pancreatic nodules, grossly normal internodular pancreas, and DSL-6 carcinoma. We observed that specific gastrin binding was absent in normal pancreas, premalignant nodules, and internodular pancreas, and also reconfirmed our previous report of marked overexpression of gastrin (CCK-B) receptors in the DSL-6 carcinoma. Specific cholecystokinin (CCK) binding was present in all pancreatic tissue types tested. Therefore, we conclude that the presence of gastrin (CCK-B) receptors in the azaserine-induced pancreatic carcinoma DSL-6, in contrast to their absence in premalignant nodules, suggests that the expression of the gastrin (CCK-B) receptor may be important in the transformation from premalignant nodules to pancreatic cancer.

Topics: Animals; Azaserine; Cell Transformation, Neoplastic; Gastrins; Male; Pancreas; Pancreatic Neoplasms; Rats; Rats, Inbred Lew; Receptors, Cholecystokinin; Sincalide