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      Long non-coding RNA NRAV enhances proliferation and invasion of hepatocellular carcinoma cells by modulating the Wnt/β-catenin signaling pathway

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      a , b , a , a , a
      Bioengineered
      Taylor & Francis
      lncRNA, NRAV, miR-199a-3p, CISD2, wnt/β-catenin, HCC

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          ABSTRACT

          Many dysregulated lncRNAs have been reported to perform an integral function in hepatocellular carcinoma (HCC). However, the role of long non-coding RNA (lncRNA) NRAV in HCC has not been elucidated. To address this issue, we investigated the function of NRAV in HCC in this research. Through bioinformatics prediction and real-time quantitative polymerase chain reaction validation, we found that NRAV plays an upmodulating role in HCC cells and tissues, and patients with high NRAV expression showed a poor prognosis. Cell viability was examined by conducting a Cell Counting Kit-8 analysis. Subsequently, the proliferation capacity of the cells was analyzed utilizing cell colony formation assay, and transwell invasion experiments were conducted to identify the cell invasion ability. To determine the association between NRAV and miR-199a-3p, and CDGSH iron-sulfur domain-containing protein 2 (CISD2), we conducted a dual luciferase assay. The protein and gene expressions were estimated utilizing Western blot. Findings illustrated that the overexpression of NRAV enhanced the HCC cell viability, proliferation and invasion, whereas they were inhibited significantly by down expression of NRAV. The dual-luciferase assay showed that miR-199a-3p is not only a target for NRAV but also interacts with the 3' UTR of CISD2 in HCC cells. MiR-199a-3p/CISD2 axis performs a function in NRAV-mediated cell behavior regulation. NRAV may trigger the Wnt/β-catenin signaling via the modulation of the miR-199a-3p/CISD2 axis in HCC. The findings of this work can provide novel insights into clinical diagnosis and the treatment of HCC in the future.

          Abbreviations: HCC, hepatocellular carcinoma; LncRNA, long non-coding RNA; CISD2, CDGSH iron-sulfur domain-containing protein 2; CCK-8, Cell Counting Kit-8; cDNA, single‐stranded complementary DNA; RT-qPCR, real-time quantitative polymerase chain reaction; BCA, bicinchoninic acid; ceRNA, competing endogenous RNAs.

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          Most cited references42

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          Cancer statistics, 2020

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.
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            starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data

            Although microRNAs (miRNAs), other non-coding RNAs (ncRNAs) (e.g. lncRNAs, pseudogenes and circRNAs) and competing endogenous RNAs (ceRNAs) have been implicated in cell-fate determination and in various human diseases, surprisingly little is known about the regulatory interaction networks among the multiple classes of RNAs. In this study, we developed starBase v2.0 (http://starbase.sysu.edu.cn/) to systematically identify the RNA–RNA and protein–RNA interaction networks from 108 CLIP-Seq (PAR-CLIP, HITS-CLIP, iCLIP, CLASH) data sets generated by 37 independent studies. By analyzing millions of RNA-binding protein binding sites, we identified ∼9000 miRNA-circRNA, 16 000 miRNA-pseudogene and 285 000 protein–RNA regulatory relationships. Moreover, starBase v2.0 has been updated to provide the most comprehensive CLIP-Seq experimentally supported miRNA-mRNA and miRNA-lncRNA interaction networks to date. We identified ∼10 000 ceRNA pairs from CLIP-supported miRNA target sites. By combining 13 functional genomic annotations, we developed miRFunction and ceRNAFunction web servers to predict the function of miRNAs and other ncRNAs from the miRNA-mediated regulatory networks. Finally, we developed interactive web implementations to provide visualization, analysis and downloading of the aforementioned large-scale data sets. This study will greatly expand our understanding of ncRNA functions and their coordinated regulatory networks.
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              Functional Classification and Experimental Dissection of Long Noncoding RNAs

              Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of DNA regulatory elements, such as enhancers and promoters, regularly initiate bidirectional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the lncRNA field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating lncRNA function. We categorize lncRNA loci into those that regulate gene expression in cis versus those that perform functions in trans , and propose an experimental approach to dissect lncRNA activity based on these classifications. These strategies to further understand lncRNAs promise to reveal new and unanticipated biology, with great potential to advance our understanding of normal physiology and disease.
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                Author and article information

                Journal
                Bioengineered
                Bioengineered
                Bioengineered
                Taylor & Francis
                2165-5979
                2165-5987
                18 April 2022
                2022
                18 April 2022
                : 13
                : 4
                : 10026-10037
                Affiliations
                [a ]Department of Oncology, Tangshan City Hospital of Traditional Chinese Medicine; , Hebei, China
                [b ]Internal Medicine of Chinese Medicine, North China University of Science and Technology; , Hebei, China
                Author notes
                CONTACT Qingxian Wang Wangqingxian2678@ 123456163.com Department of Oncology, Tangshan City Hospital of Traditional Chinese Medicine; , Hebei 063000, China
                [#]

                The first two authors contributed equally.

                Article
                2062977
                10.1080/21655979.2022.2062977
                9161990
                35436415
                0e1a9d8a-1259-4a2e-be39-6de026d82ec7
                © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 6, References: 42, Pages: 12
                Categories
                Research Article
                Research Paper

                Biomedical engineering
                lncrna,nrav,mir-199a-3p,cisd2,wnt/β-catenin,hcc
                Biomedical engineering
                lncrna, nrav, mir-199a-3p, cisd2, wnt/β-catenin, hcc

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