Abstract. Human epidermal growth factor receptor 2 (HER-2) has an important clinical role in various cancers. However, the prognostic impact of HER-2 in gastric cancer (GC) is controversial. RAB1A is an important small molecule in the mechanistic target of rapamycin signalling pathway, which is one of the downstream signalling pathways of the epidermal growth factor receptor family. In recent years, the aberrant expression of RAB1A has been reported in a number of tumours, but its regulation in GC has not been extensively examined. Therefore, the present study investigated the expression pattern and prognostic significance of HER-2 and RAB1A in gastric adenocarcinoma (CAG). A comprehensive analysis was performed to examine the expression level of HER-2 and RAB1A in 280 cases of paired paraffin-embedded GAC tissues and an additional 120 archived GAC tissue samples. HER-2 and RAB1A protein expression was assessed by immunohistochemistry and cases with a 2+ score for HER-2 expression levels were subjected to fluorescence in situ hybridization to determine the HER-2 amplification status. Furthermore, HER-2 and RAB1A mRNA expression was quantified by reverse transcription-quantitative polymerase chain reaction. The comparison of continuous data between two groups was performed using a paired-samples t-test. Clinical correlations were determined using Pearson's Chi-square and Fisher's exact tests. Kaplan-Meier survival curves were used to estimate overall survival (OS). Cox proportional hazards models were used to determine associations between HER-2 and RAB1A expression and outcomes. Regression analyses were performed to detect the correlation between the mRNA levels of HER-2 and RAB1A in GAC tissues. It was observed that RAB1A was significantly overexpressed in GAC tissues compared with normal tissues (P<0.001). Approximately 12.86% of the 280 GAC patients had HER-2 amplification. Additionally, RAB1A expression was significantly associated with a short OS (P<0.001) but there were no significant differences in survival between the HER-2 high-expression group and the HER-2 low-expression group. Additionally, the co-expression of HER-2 and RAB1A indicated poorer OS than the overexpression of each protein (P=0.001), and the two factors were significantly positively correlated in GAC (P= 0.012). These findings may be used to further explore the molecular mechanisms and regulatory associations among signalling pathways in GC.
Exosomes carry functional molecules that can regulate cancer progression. Understanding the function of exosomal markers may provide invaluable insights into the mechanism of metastasis in hepatocellular carcinoma (HCC). The aim of the present study was to identify metastasis-associated microRNAs (miRNAs/miRs) expressed in plasma exosomes. A miRNA microarray and reverse transcription-quantitative PCR were used to analyze the plasma exosome miRNA expression profiles of patients with metastatic or non-metastatic HCC. Receiver operating characteristic (ROC) curve and Kaplan-Meier analyses were used to evaluate the predictive performance and prognostic efficacy of candidate miRNAs identified in the Gene Expression Omnibus database (dataset accession no. GSE67140). Bioinformatics analysis was used to examine the role of exosomal miRNAs in HCC metastasis. A total of 32 miRNAs were differentially expressed in plasma exosomes of patients with metastatic HCC compared with in those of patients with non-metastatic HCC. Additionally, the expression levels of six miRNAs were consistent between plasma exosome samples and matched tissue samples. ROC analysis demonstrated that miR-18a, miR-27a and miR-20b could discriminate metastatic HCC from non-metastatic HCC. Furthermore, the prognostic efficacy of the combination of three miRNAs (miR-18a, miR-20b and miR-221) was superior to that of individual miRNAs. Survival analysis demonstrated that high expression levels of the candidate miRNAs were associated with poor prognosis. Bioinformatics analysis indicated that the potential target genes of these miRNAs were involved in biological processes, molecular functions and cellular components that were associated with metastasis. The present findings suggested that these exosomal miRNAs may serve important roles in HCC lung metastasis and could represent a complementary clinical tool for the assessment of HCC prognosis.
Background: The mammalian target of rapamycin complex 1 (mTORC1) is a pivotal regulator of cell growth and proliferation in response to nutrition and various factor. In recent years, studies have focus on over-activation of mTORC1 in normal cells leading to tumorigenesis and malignant tumor development. However, the precise factors of mTORC1 hyperactivation to promote the growth of hepatocellular carcinoma (HCC) or other cancers are still not well characterized. Thus, in this study, we aimed to clarify a novel gene -Rab1A, and it's expression and functional role in mTORC1 signal in of HCC. Methods: We analyzed the Rab1A protein in HCC and para-cancer samples from 143 patients and the correlation with its survival. To identify Rab1A's role in tumor progression, a serious of functional study were applied including overexpression and knockdown Rab1A in different cell lines both in vivo and in vitro. For mechanism research, western bolt was demonstrated to identify the signal dysregulation between Rab1A abnormity and mTORC1 pathway under involvement of irritants. Results: Our results showed that, compared with normal livers, Rab1A was frequently overexpressed in HCC and significantly associated with HCC prognosis. Functional study demonstrated that overexpression of Rab1A in HCC cells increased cell growth, cell migration, cell cycle progression and tumor formation in vivo and/or in vitro, all of which were effectively inhibited when Rab1A was silenced by shRNA. We further provided evidences that Rab1A promotes HCC growth and migration through phosphorylation of S6K, the consequence of activating mTORC1 signaling pathway. Mechanism research of the signal pathway between Rab1A and mTORC1 suggest that Rab1A is likely to stimulate mTORC1 directly, with the cooperation of Amino acid stimulation but not depend on the pathway of PI3K/AKT and MAPK/ERK.. Citation Format: Bi-Hong Xu, Xiao-Xing Li, Hui-yun Wang, X.F. Steven Zheng. Overexpressed Rab1A is associated poor prognosis and promotes oncogenic growth and metastasis through mTORC1 activation in hepatocellular carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2053. doi:10.1158/1538-7445.AM2015-2053
Background: Oxidative stress is an important factor in the modulation of both tumorigenesis and anticancer responses. Ozone (O 3 ) is a strong oxidant that causes redox reactions and exerts anticancer effects in various types of cancer cells. However, the pathways involved in O 3 -induced cell death are not well understood. Methods: In vitro human hepatocellular carcinoma (HCC) BEL7402 cells were treated with various O 3 concentrations to evaluate O 3 cytotoxicity by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The regulatory mechanisms were analyzed by western blot analysis. In vivo, an HCC model was established to evaluate the inhibition of HCC with O 3 treatment. Results: In vitro cells treated with O 3 exhibited a round and small morphology with nuclear shrinkage and fragmentation. The CCK-8 assay confirmed the potent cytotoxic activity of O 3 against BEL7402 cells (IC 50 value of 5 μg/mL). Acridine orange/ethidium bromide (AO/EB) staining revealed apoptosis of BEL7402 cells after O 3 treatment. Flow cytometry analysis showed that S phase cell cycle arrest and apoptosis increased with O 3 exposure. In addition, O3 exposure reduced the mitochondrial membrane potential (ΔΨm) and induced reactive oxygen species (ROS) accumulation. Western blot analysis showed that O 3 exposure reduced B-cell lymphoma 2 (BCL-2) expression and increased cleaved poly ADP-ribose polymerase (PARP), cytochrome C (Cyt-C), caspase-3, caspase-9, and p-JNK expression. In vivo, treatment with intratumor injection O 3 (20 μg/mL) inhibited HCC growth.Conclusions: Overall, our findings showed that O 3 induces BEL7402 cell apoptosis via the intrinsic mitochondria-dependent pathway. Therefore, O 3 has therapeutic potential for HCC.
Background Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. High-mobility group box 1 (HMGB1), a highly conserved chromosome protein, is considered as a potential therapeutic target and novel biomarker because of its regulation in the proliferation and metastasis of HCC. Ozone has been shown to be beneficial in the treatment of cancer. The objective of this study was to explore the effects and molecular mechanism of ozonated water on the proliferation, migration, and invasion of BEL7402 HCC cells. Materials and Methods We assessed cell proliferation using a CCK-8 assay kit and flow cytometry; we performed wound healing and transwell assays to evaluate the effects of ozonated water treatment on cell invasion and migration. We determined reactive oxygen species (ROS) values by flow cytometry and used ELISAs to detect cytokines HMGB1, IL-6, and TNF-α. In addition, we assessed mRNA and protein cytokine expressions using RT-qPCR and Western blot. Results Ozonated water decreased the viability of the HCC cells; the IC50 of ozonated water at 24 h was approximately 1.5 μg/mL. Compared with control groups, ozone treated cells revealed reduced mobility on wound healing assays and decreased invasion in transwell assays. HMGB1, IL-6, and TNF-α cytokines were found at lower levels in ozone treated cells than in control cells. Ozonated water-induced ROS accumulation. Likewise, the expressions of phosphorylated nuclear factor Kappa B (NF-κB), p65, NF-κB, P-STAT3, IL-6, JAK2, Slug, Twist, vimentin, MMP-2, MMP-9, and HMGB1 were decreased in the treated cells. Conclusion Our findings suggest that ozonated water inhibits the proliferation, invasion, and metastasis of HCC cells via regulation of the HMGB1/NF-κB/STAT3 signaling pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.