sincalide and Carcinogenesis

Polyrhachis vicina Roger (P. vicina), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis, hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia. Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored.. The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets.. To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment.. Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL.. According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

Topics: Animals; Carcinogenesis; Colorectal Neoplasms; Molecular Docking Simulation; Necroptosis; Sincalide

Pancreatic cancer is a prevalent malignancy of the digestive system and a major cause of cancer-associated deaths. Previous studies have shown that mutation in the dermokine-β (DMKN-β) gene causes pancreatic and colorectal cancer. The role of the carboxy-terminal domain of DMKN-β and dermokine-α (DMKN-α) genes in cancer tumorigenesis. Herein, the role of DMKN-α in pancreatic cancer (PC) tumorigenesis and the mechanisms underlying this process were investigated. Differentially expressed genes between PC and matched normal cells were identified through RNA-seq analysis, and the corresponding protein expression levels were verified using Western blot analysis. In vivo tumor formation experiment was also performed in nude mice. We found that the DMKN-α gene was overexpressed in cancerous pancreatic cell lines compared to normal pancreatic cell lines. CCK-8, colony formation, RTCA test, wound healing, as well as transwell test showed that the overexpression of DMKN-α enhanced the proliferation, migration, invasion, and EMT of PC cells. In vivo assays confirmed that DMKN-α promotes tumorigenesis. The findings of this study show that DMKN-α is a potential oncogene for pancreatic cancer.

Topics: Animals; Carcinogenesis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Intercellular Signaling Peptides and Proteins; Mice; Mice, Nude; Neoplasm Invasiveness; Pancreatic Neoplasms; Sincalide

The study aimed to explore tumor suppressor mechanism of ARNTL from the perspective of autophagy in oral cancer. Human oral squamous carcinoma HN6 cells stably overexpressing ARNTL were established, cell viability and apoptosis were detected by CCK-8 and TUNEL assays, and intracellular autophagosomes were observed under electron microscopy. Western Blot detected expressions of Beclin1, LC3 II/I, ATG-12, P62, BAX and BCL-2. Bafilomycin A1 was used to detect autophagic flux, and Western Blot was used to detect changes of LC3II and P62 proteins. Autophinib was added to cells with ARNTL overexpression for recovery experiments, and cell proliferation and apoptosis were detected by flow cytometry. In vivo tumorigenesis experiment was used to evaluate the in vivo anti-tumor efficacy of ARNTL, and Western blot simultaneously detected ARNTL, LC3 II/I, Beclin1, P62 and ATG-12 expressions. ARNTL overexpression promoted apoptosis and autophagy and inhibited cell viability. In ARNTL-overexpressing cells, expressions of Beclin1, LC3 II/I, and BAX were significantly up-regulated, while P62 and BCL-2 expressions were decreased, and ATG-12 expression wasn't significantly changed. When the autophagy inhibitor Autophinib was used, expressions of elevated BAX and decreased BCL-2 were reversed effectively, as were decreased cell proliferation index and increased apoptosis index. An in vivo tumorigenesis assay also showed ARNTL overexpression inhibited tumor growth, and autophagy-related protein expressions were consistent with the in vitro data. The research demonstrated for the first time that ARNTL induced apoptosis and inhibited cell proliferation dependent on autophagy in oral cancer, which provides theoretical basis for potential therapeutic targets.

Topics: Apoptosis; ARNTL Transcription Factors; Autophagy; bcl-2-Associated X Protein; Beclin-1; Carcinogenesis; Cell Line, Tumor; Circadian Clocks; Humans; Mouth Neoplasms; Proto-Oncogene Proteins c-bcl-2; Sincalide

Studies summarize that LINC00958 manifests considerable oncogenic potential in diverse cancers. However, its role in colon cancer (CC) is rarely studied. Herein, we attempted to disclose LINC00958's mechanism of action and function in the development of CC.. The relative expressions of LINC00958, CDK1 mRNA, and miR-145-3p were quantified by means of RT-qPCR. CDK1 protein levels were determined via western blotting. CCK-8, wound healing, and transwell experiments were conducted to assess the abilities of cells to proliferate, migrate, and invade. To ascertain the role of LINC00958,. A reinforced expression of LINC00958 was observed among CC cells and tumor samples. The deficiency in LINC00958 not only restrained the invasion, migration, and proliferation of the cancer cells but also impeded the development of tumors. LINC00958 interacts with miR-145-3p and modulates the miR-145-3p/CDK1 axis. Hence, LINC00958 contributes to CC's malignant progression.

Topics: Carcinogenesis; CDC2 Protein Kinase; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; RNA, Long Noncoding; RNA, Messenger; Sincalide

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

Circular RNA of vimentin (circ-VIM) is a predictor for poor prognosis of acute myeloid leukemia, but we had little information on its function in esophageal cancer (EC). Here we examined the effects of circ-VIM together with sevoflurane on immune escape and multiple oncogenic activities of EC.. Significant upregulation of circ-VIM and PD-L1 and downregulation of miR-124 were detected in EC tissues or cells. Circ-VIM sponged miR-124 and released its suppression on the downstream target PD-L1. Sevoflurane, independent of circ-VIM, also upregulated miR-124 to lower PD-L1 expression. By modulating miR-124/PD-L1 axis, silencing circ-VIM and applying sevoflurane both inhibited immune escape and multiple oncogenic activities of EC in vitro, and suppressed xenograft growth and lung metastases in vivo. The inactivation of Ras/ERK signaling pathway was involved in suppression of malignant phenotypes by silencing circ-VIM and sevoflurane treatment.. Silencing circ-VIM and applying sevoflurane, by separately regulating miR-124/PD-L1 axis, presented synergistic effects in inhibiting immune escape and multiple malignant phenotypes of EC cells.

Topics: Annexin A5; B7-H1 Antigen; Carcinogenesis; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cell Movement; Cell Proliferation; Esophageal Neoplasms; Humans; Lung Neoplasms; MicroRNAs; RNA, Circular; Sevoflurane; Sincalide; Vimentin

The poor prognosis of esophagus cancer (EC) is mainly due to its high invasiveness and metastasis, so it is urgent to search effectively prognostic markers and explore their roles in the mechanism of metastasis.. Based on the TCGA database, we downloaded the RNA-Seq for analyzing the expression of ATP6V0D2. QRT-PCR was used to test the mRNA levels of ATP6V0D2 in cell lines. Chi-square tests were used to evaluate the correlation between ATP6V0D2 and clinical characteristics. Prognostic values were determined by Kaplan-Meier methods and cox's regression models. CCK-8 and clone formation assays were employed to evaluate the cell viability, and Transwell assay was implemented to determine the invasive and migratory abilities. Correlations between ATP6V0D2 and motion-related markers were analyzed by the GEPIA database and confirmed by western blot. Moreover, the relationship between ATP6V0D2 and molecules related to cell cycle and apoptosis was also determined by western blot.. A significant increase was observed in 3 EC-related cell lines compared to the normal cell line. ATP6V0D2 has a connection with the poor prognosis and can be considered as an independent prognosticator for patients with EC. Besides, ATP6V0D2 can improve cells viability as well as invasive and migratory abilities. What's more, downregulation of ATP6V0D2 notably enhanced E-cadherin expression, while decreased N-cadherin, Vimentin, and MMP9 expression, whereas overexpression of ATP6V0D2 presented the opposite outcomes. Furthermore, we found that silencing ATP6V0D2 led to a significant reduction on the protein expression of Cyclin D1, CDK4, Bcl-2, whereas resulted in a notable enhancement on the Bax level.. ATP6V0D2 might be an independent prognosticator for EC patients, and it possibly promotes tumorigenesis by regulating epithelial-mesenchymal transition, cell cycle and apoptosis-related markers, providing the possibility that ATP6V0D2 may be a novel biomarker for the therapeutic intervention of EC.

Topics: Apoptosis; Biomarkers, Tumor; Cadherins; Carcinogenesis; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Survival; Cyclin D1; Cyclin-Dependent Kinase 4; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Female; Genes, bcl-2; Humans; Male; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Protons; RNA, Messenger; Sincalide; Vacuolar Proton-Translocating ATPases; Vimentin

Kallmann syndrome 1 sequence gene (KAL1) protein is an extracellular matrix associated protein which plays vital roles in neurons development and cell migration. However, its biological functions and clinical implications have yet not been revealed in oral carcinogenesis. The objective of the study was to evaluate the role of KAL1 in oral cancer and determine clinical significance of KAL1 in oral squamous cell carcinomas (OSCCs).. The expression pattern of KAL1 was examined in a testing cohort including OSCCs (n = 42) and paired adjacent tissues (PATs) (n = 14) by real-time PCR. The result was further validated in a validating cohort of OSCCs (n = 32). Correlation between clinicopathological parameters and KAL1 mRNA levels was analyzed by Kruskal-Wallis test. In vitro, the effects of KAL1 ablation through siRNA-mediated knockdown on the proliferation of OSCC cells were determined by CCK-8, BrdU, and colonies formation assays, respectively. In addition, cell cycle distribution was further evaluated by cytometry.. We observed that remarkably decreased expression of KAL1 mRNA in two independent cohorts (P = 0.0002 and P = 0.033, respectively). Furthermore, downregulated KAL1 mRNA was significantly associated with worse pathological grade (P = 0.013 and P = 0.035, respectively). Upon KAL1 silencing, the proliferation and colonies formation potentials of OSCC cells were notably promoted by accelerating G1 to M phase transition.. These data indicated that KAL1 plays a potential suppressive role on OSCC initiation and progression, and KAL1 gene may serve as an adjuvant biomarker for the identification of pathological grade.

Topics: Bromodeoxyuridine; Carcinogenesis; Carcinoma, Squamous Cell; Cell Culture Techniques; Cell Cycle Checkpoints; Cell Differentiation; Cell Division; Cell Line, Tumor; Cell Proliferation; Cohort Studies; Disease Progression; Extracellular Matrix Proteins; Female; G1 Phase; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Gene Silencing; Humans; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Neoplasm Grading; Nerve Tissue Proteins; RNA, Small Interfering; Sincalide; Tumor Suppressor Proteins

Androgen receptor (AR) is critical for prostate tumorigenesis and is frequently overexpressed during prostate cancer (PC) progression. However, few studies have addressed the epigenetic regulation of AR expression.. We analyzed SMYD3 expression in human PC with Western blot and immunohistochemistry. SMYD3 expression was knocked down using short hairpin RNA (shRNA) or small interfering RNA (siRNA). Cell proliferation, colony formation, and apoptosis analyses and xenograft transplantation were performed to evaluate the impact of SMYD3 depletion on PC cells. AR expression and promoter activity were determined using real-time quantitative polymerase chain reaction, western blot, and luciferase reporter assay. AR promoter association with Sp1, SMYD3, and histone modifications was assessed by chromatin immunoprecipitation. Differences in AR mRNA abundance and promoter activity were analyzed using Wilcoxon signed-rank tests, SMYD3 expression was analyzed using with Mann-Whitney U tests for unpaired samples, and tumor weight was analyzed with Student t test. All statistical tests were two-sided.. The upregulation of SMYD3 protein expression was observed in seven of eight prostate tumor specimens, compared with matched normal tissues. Immunohistochemical analysis showed a strong SMYD3 staining in the nuclei of PC tissues in eight of 25 (32%) cases and in the cytoplasm in 23 out of 25 (92%) cases, whereas benign prostate tissue exhibited weak immunostaining. Depletion of SMYD3 by siRNA or shRNA inhibited PC cell proliferation (72 hours relative to 24 hours: control shRNA vs SMYD3 shRNA 1: mean fold change = 2.76 vs 1.68; difference = 1.08; 95% confidence interval = 0.78 to 1.38, P < .001), colony formation, cell migration, invasion, and xenograft tumor formation. Two functional SMYD3-binding motifs were identified in the AR promoter region.. SMYD3 promotes prostate tumorigenesis and mediates epigenetic upregulation of AR expression.

Topics: Carcinogenesis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chromatin Immunoprecipitation; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Histone-Lysine N-Methyltransferase; Humans; Immunoblotting; Immunohistochemistry; Male; Neoplasm Invasiveness; Promoter Regions, Genetic; Prostatic Neoplasms, Castration-Resistant; Real-Time Polymerase Chain Reaction; Receptors, Androgen; RNA, Small Interfering; Sincalide; Transcription, Genetic; Transfection; Up-Regulation; Xenograft Model Antitumor Assays