Gastric cancer (GC) has one of the highest mortality rates of malignancies globally. Currently, ciRS-7, a novel circular RNA, has emerged as a potential sponge for miR-7. However, few studies on ciRS-7 in GC have been performed. In this study, we investigated the clinical significance and function of ciRS-7 in GC. First, the expression levels of ciRS-7 in 102 primary GC tissues and the matched para-carcinoma tissues were evaluated and the clinical relevance was confirmed in an independent validation cohort (n = 154). Second, the effects of ciRS-7 on miR-7, PTEN, and PI3K were evaluated. Finally, the function of ciRS-7 in GC was analyzed with cell lines and nude mice. The expression of ciRS-7 was significantly upregulated in GC tissues compared with the matched para-carcinoma tissues (P = 0.0023), and the upregulation of ciRS-7 was linked to poor survival in the testing (P = 0.0143) and validation cohort (P = 0.0061). Multivariate survival analysis revealed that ciRS-7 was probably an independent risk factor of overall survival (P < 0.05). Furthermore, overexpression of ciRS-7 blocked the miR-7-induced tumor suppression in MGC-803 and HGC-27 cells and led to a more aggressive oncogenic phenotype, via antagonizing miR-7-mediated PTEN/PI3K/AKT pathway. ciRS-7 may act as a prospective prognostic biological marker and a promising therapeutic target for GC. J. Cell. Biochem. 119: 440-446, 2018. © 2017 Wiley Periodicals, Inc.

Overexpression of Circular RNA ciRS-7 Abrogates the Tumor Suppressive Effect of miR-7 on Gastric Cancer via PTEN/PI3K/AKT Signaling Pathway.

VDAC1, mitochondrial dysfunction, and Alzheimer's disease.

Cancer and neurodegeneration are different classes of diseases that share the involvement of mitochondria in their pathogenesis. Whereas the high glycolytic rate (the so-called Warburg metabolism) and the suppression of apoptosis are key elements for the establishment and maintenance of cancer cells, mitochondrial dysfunction and increased cell death mark neurodegeneration. As a main actor in the regulation of cell metabolism and apoptosis, VDAC may represent the common point between these two broad families of pathologies. Located in the outer mitochondrial membrane, VDAC forms channels that control the flux of ions and metabolites across the mitochondrion thus mediating the organelle's cross-talk with the rest of the cell. Furthermore, the interaction with both pro-apoptotic and anti-apoptotic factors makes VDAC a gatekeeper for mitochondria-mediated cell death and survival signaling pathways. Unfortunately, the lack of an evident druggability of this protein, since it has no defined binding or active sites, makes the quest for VDAC interacting molecules a difficult tale. Pharmacologically active molecules of different classes have been proposed to hit cancer and neurodegeneration. In this work, we provide an exhaustive and detailed survey of all the molecules, peptides, and microRNAs that exploit VDAC in the treatment of the two examined classes of pathologies. The mechanism of action and the potential or effectiveness of each compound are discussed.

VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis

The voltage-dependent anion channel 1 (VDAC1) protein, is an important regulator of mitochondrial function, and serves as a mitochondrial gatekeeper, with responsibility for cellular fate. In addition to control over energy sources and metabolism, the protein also regulates epigenomic elements and apoptosis via mediating the release of apoptotic proteins from the mitochondria. Apoptotic and pathological conditions, as well as certain viruses, induce cell death by inducing VDAC1 overexpression leading to oligomerization, and the formation of a large channel within the VDAC1 homo-oligomer. This then permits the release of pro-apoptotic proteins from the mitochondria and subsequent apoptosis. Mitochondrial DNA can also be released through this channel, which triggers type-Ι interferon responses. VDAC1 also participates in endoplasmic reticulum (ER)-mitochondria cross-talk, and in the regulation of autophagy, and inflammation. Its location in the outer mitochondrial membrane, makes VDAC1 ideally placed to interact with over 100 proteins, and to orchestrate the interaction of mitochondrial and cellular activities through a number of signaling pathways. Here, we provide insights into the multiple functions of VDAC1 and describe its involvement in several diseases, which demonstrate the potential of this protein as a druggable target in a wide variety of pathologies, including cancer.

https://www.mdpi.com/2218-273X/10/11/1485/pdf

VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases.

This review presents current knowledge related to VDAC1 as a multi-functional mitochondrial protein acting on both sides of the coin, regulating cell life and death, and highlighting these functions in relation to disease. It is now recognized that VDAC1 does not only play a crucial role in regulating the metabolic and energetic functions of mitochondria. The location of VDAC1 at the outer mitochondrial membrane (OMM) allows the control of metabolic cross-talk between mitochondria and the rest of the cell and also enables its interaction with proteins involved in metabolic and survival pathways. Along with regulating cellular energy production and metabolism, VDAC1 is also involved in the process of mitochondria-mediated apoptosis by mediating the release of apoptotic proteins and interacting with anti-apoptotic proteins. VDAC1 functions in the release of apoptotic proteins located in the mitochondrion inter-membranal space via oligomerization to form a large channel that allows passage of cytochrome c and AIF and their release to the cytosol, subsequently apoptotic cell death. VDAC1 also regulates apoptosis via interactions with apoptosis regulatory proteins, such as hexokinase (HK), Bcl2 and Bcl-xL, some of which are also highly expressed in many cancers. This review also provide insight into VDAC1 function in Ca2+ homeostasis, oxidative stress, and presents VDAC1 as a hub protein interacting with over 100 proteins. Such interactions enable VDAC1 to mediate and regulate the integration of mitochondrial functions with cellular activities. VDAC1 can thus be considered as standing at the crossroads between mitochondrial metabolite transport and apoptosis and hence represents an emerging cancer drug target.

VDAC1 at the crossroads of cell metabolism, apoptosis and cell stress.

Recent studies have been shown that voltage-dependent anion channel 1 (VDAC1) plays an important role in carcinogenesis. However, its molecular biological function in hepatocellular carcinoma (HCC) has not been entirely clarified. This study investigated the expression of VDAC1 in HCC and its prognostic value for HCC patients. Furthermore, we also identify the relevant VDAC1 direct target. Western blot, real-time quantitative PCR (qRT-PCR), and immunohistochemical (IHC) staining were performed to detect the expression of VDAC1 in HCC. Furthermore, the relationship between the VDAC1 level and clinicopathological features and prognostic values was explored. The effects of VDAC1 on HCC cell proliferation, migration, and invasion were also investigated in vitro. Predicted target gene of VDAC1 was determined by dual-luciferase reporter assay, qRT-PCR, and Western blot analyses. Our results revealed elevated VDAC1 messenger RNA (mRNA) (P = 0.0020) and protein (P = 0.0035) expression in tumor tissue samples compared with paired adjacent non-tumorous tissue samples. High VDAC1 expression was correlated with distant metastasis (P = 0.025), differentiation (P = 0.002), and advanced tumor stage (P = 0.004) in HCC patients. Kaplan-Meier survival analysis demonstrated that high expression of VDAC1 was significantly correlated with a poor prognosis for HCC patients (P < 0.001). The multivariate analysis revealed that VDAC1 expression was an independent prognostic factor of the overall survival rate of HCC patients. Furthermore, knockdown of VDAC1 inhibits HCC cell proliferation, migration, and invasion in vitro. Moreover, further study revealed that miR-7 was a putative target of VDAC1. Our study suggested that miR-7 suppressed the expression of VDAC1. VDAC1 plays an important role in tumor progression and may be used as a potential role in the prognosis of HCC patients.

MicroRNA-7 downregulates the oncogene VDAC1 to influence hepatocellular carcinoma proliferation and metastasis

Purpose: To investigate the risk factors for recurrence and treatment strategies after patients with hepatocellular carcinoma (HCC) undergo total laparoscopic hepatectomy (LH). Methods: The study included 109 patients who underwent LH (laparoscopy resection [LR] group, n = 50) or open hepatectomy [OH] (open resection [OR] group, n = 59) for HCC in our hospital between March 2011 and June 2016. Perioperative outcomes, disease recurrence, survival, and risk factors for recurrence were analyzed. Results: Patient characteristics did not significantly differ between groups. The 1- and 3-year survival rates were 90.7% and 78.1%, respectively, for the LR group and 83.1% and 74.4%, respectively, for the OR group (P = .71). The 1- and 3-year disease-free survival rates were 89.6% and 51.4%, respectively, for the LR group and 84.7% and 59.6%, respectively, for the OR group (P = .935). Tumor size, differentiation, vascular invasion, surgical bleeding, and surgical resection margin were risk factors for tumo...

/pdf/recurrence-of-hepatocellular-carcinoma-after-laparoscopic-4bqemvbyyy.pdf

Recurrence of Hepatocellular Carcinoma After Laparoscopic Hepatectomy: Risk Factors and Treatment Strategies.

Background Hepatocellular carcinoma (HCC) is an aggressive malignant tumor with poor prognosis that is characterized by high rates of postoperative recurrence and mortality. Understanding the molecular mechanism of this malignancy is of great significance for the development of new and effective strategies for the treatment of hepatocellular carcinoma. Thyroid hormone receptor-interacting protein 6 (TRIP6), also known as zyxin-related protein-1 or ZRP-1, is an adaptor protein that belongs to the zyxin family of LIM proteins. Recent studies showed that TRIP6 is involved in carcinogenesis. But the functional role of TRIP6 in HCC has not been reported to date. Methods: TRIP6 expression level in HCC cell lines and normal cell line was measured by qPCR. The roles of TRIP6 on HCC cell proliferation, colony formation, and invasion were examined by MTT assay, colony formation assay, and transwell invasion assay, respectively. The effect of TRIP6 on the overall survival of HCC patients was further analyzed. ChIP assay and western blot were performed to validate whether FOXC1 was involved in the regulation of TRIP6 expression. Results Western blot and immunohistochemical analyses showed that TRIP6 expression was up-regulated in HCC tissues compared with adjacent non-tumor tissues. Kaplan-Meier survival analysis indicated that upregulation of TRIP6 was dramatically associated with poor overall survival. TRIP6 knockdown significantly inhibited cell migration, invasion, and proliferation, and its effect on cell proliferation was mediated by the modulation of cell cycle progression. FOXC1 also played a vital role in TRIP6 regulation. TRIP6 mediated the FOXC1-regulated proliferation, invasion, and migration in vitro and tumor growth in vivo. Conclusions These results suggest that TRIP6 may contribute to the invasiveness and metastasis of HCC cells, and provide new insight into the crucial role of TRIP6 in tumorigenesis and cancer progression.

TRIP6 promotes tumorigenic capability through regulating FOXC1 in hepatocellular carcinoma.

Background Circular RNAs (circRNAs), a novel type of non-coding RNA, play a vital role in the pathogenesis and development of cancer. CircRNAs signatures may be useful as prognostic and predictive factors as well as clinical tools for evaluating disease status and prognosis. This study was carried out to explore novel circRNA signatures in hepatocellular carcinoma (HCC). Methods The expression profiles of circRNAs were retrieved from the Gene Expression Omnibus (GEO). The expression profiles of miRNAs and mRNAs were obtained from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The results of the microarray were validated by quantitative real-time RCR (qPCR). Based on circRNA-miRNA pairs and miRNA-mRNA pairs, a competitive endogenous RNA (ceRNA) network was constructed. Functional analysis was performed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA). Furthermore, survival analysis was carried out using the Kaplan-Meier curve and the log-rank test. Results Differentially expressed circRNAs in HCC from GEO databases (GSE94508 and GSE97332) were screened and analyzed using the bioinformatics method. We detected a total of 26 differentially expressed circRNAs by qPCR and then selected 6 circRNAs to construct the circRNA-miRNA-mRNA networks. Through prognostic analysis, 3 target hub genes (AURKA, KIF5B, and RHOA) of circRNAs were discovered. Moreover, GSEA and GSVA were used to reveal the functions of AURKA, KIF5B, and RHOA in HCC. Conclusions We identified three hub genes, and our results suggest that the circHMGCS1/miR-581/AURKA, circHMGCS1/miR-892a/KIF5B, and circTMCO3/miR-577/RHOA axes may play a vital role in HCC progression.

/pdf/identification-and-integrated-analysis-of-hepatocellular-3i186jx2qk.pdf

Identification and integrated analysis of hepatocellular carcinoma-related circular RNA signature

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Feiran Wang

Author Tools

Chat about Author

Papers

MicroRNA-7 downregulates the oncogene VDAC1 to influence hepatocellular carcinoma proliferation and metastasis

Recurrence of Hepatocellular Carcinoma After Laparoscopic Hepatectomy: Risk Factors and Treatment Strategies.

TRIP6 promotes tumorigenic capability through regulating FOXC1 in hepatocellular carcinoma.

Identification and integrated analysis of hepatocellular carcinoma-related circular RNA signature