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      • Record: found
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      PIWIL2 promotes progression of non-small cell lung cancer by inducing CDK2 and Cyclin A expression

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          Abstract

          Background

          PIWI proteins have important roles in tumorigenesis due to their interaction with piRNAs. Recent studies suggest that PIWI proteins affect prognosis of various cancers.

          Methods

          In the present study, PIWI genes expression was assayed in non-small cell lung cancer (NSCLC). To determine the effects of PIWIL2 on NSCLC cells, overexpression and interference assays were performed using the A549 and H460 cell lines. The tumor formation model was performed to demonstrate the effects of PIWIL2 on tumor formation in vivo.

          Results

          PIWIL2 was increased both at the RNA and protein level in malignant cancer tissues compared with adjacent normal tissue. Moreover, increased PIWIL2 gene expression was negatively correlated with prognosis in NSCLC patients. Overexpression and interference of PIWIL2 promoted and depressed cell proliferation, respectively. Meanwhile, PIWIL2 interference arrested cells at the G2/M stage. In addition, we found that CDK2 and Cyclin A expression were correlated with PIWIL2 expression. Moreover, transfection of PIWIL2 promoted tumor growth in nude mice.

          Conclusion

          Our findings shed light on the function of PIWIL2 in NSCLC and suggest potential prognostic and therapeutic value.

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          Most cited references37

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          Epigenetics in cancer.

          S. Sharma, T. Kelly, P. Jones (2010)
          Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Global changes in the epigenetic landscape are a hallmark of cancer. The initiation and progression of cancer, traditionally seen as a genetic disease, is now realized to involve epigenetic abnormalities along with genetic alterations. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer including DNA methylation, histone modifications, nucleosome positioning and non-coding RNAs, specifically microRNA expression. The reversible nature of epigenetic aberrations has led to the emergence of the promising field of epigenetic therapy, which is already making progress with the recent FDA approval of three epigenetic drugs for cancer treatment. In this review, we discuss the current understanding of alterations in the epigenetic landscape that occur in cancer compared with normal cells, the roles of these changes in cancer initiation and progression, including the cancer stem cell model, and the potential use of this knowledge in designing more effective treatment strategies.
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            A germline-specific class of small RNAs binds mammalian Piwi proteins.

            Angélique Girard, Ravi Sachidanandam, Gregory Hannon … (2006)
            Small RNAs associate with Argonaute proteins and serve as sequence-specific guides to regulate messenger RNA stability, protein synthesis, chromatin organization and genome structure. In animals, Argonaute proteins segregate into two subfamilies. The Argonaute subfamily acts in RNA interference and in microRNA-mediated gene regulation using 21-22-nucleotide RNAs as guides. The Piwi subfamily is involved in germline-specific events such as germline stem cell maintenance and meiosis. However, neither the biochemical function of Piwi proteins nor the nature of their small RNA guides is known. Here we show that MIWI, a murine Piwi protein, binds a previously uncharacterized class of approximately 29-30-nucleotide RNAs that are highly abundant in testes. We have therefore named these Piwi-interacting RNAs (piRNAs). piRNAs show distinctive localization patterns in the genome, being predominantly grouped into 20-90-kilobase clusters, wherein long stretches of small RNAs are derived from only one strand. Similar piRNAs are also found in human and rat, with major clusters occurring in syntenic locations. Although their function must still be resolved, the abundance of piRNAs in germline cells and the male sterility of Miwi mutants suggest a role in gametogenesis.
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              Prognostic significance of morphologic parameters in renal cell carcinoma.

              Susan A. Fuhrman, Larry C Lasky, Catherine Limas (1982)
              The prognostic significance of morphologic parameters was evaluated in 103 patients with renal cell carcinoma diagnosed during 1961--1974. Pathologic material was classified as to pathologic stage, tumor size, cell arrangement, cell type and nuclear grade. Four nuclear grades (1--4) were defined in order of increasing nuclear size, irregularity and nucleolar prominence. Nuclear grade was more effective than each of the other parameters in predicting development of distant metastasis following nephrectomy. Among 45 patients who presented in Stage I, tumors classified as nuclear grade 1 did not metastasize for at least 5 years, whereas 50% of the higher grade tumors did so. Moreover, among Stage I tumors there was a significant difference in subsequent metastatic rate between nuclear grades 1 and 2. There was an apparent positive relationship between cell type and metastatic rate; clear cell tumors were less aggressive than predominantly granular cell tumors (metastatic rate 38% versus 71%). This relationship in part a function of the nuclear grade: only 5% of grade 3 and 4 tumors consisted of clear cells, whereas such high grades were seen in 57% of granular cell tumors. The size of the primary correlated well with the stage at the time of surgery. However, with the exception of extremely large and small tumors, the size was not useful in predicting the subsequent course of patients treated for Stage I tumors. Nuclear grade was the most significant prognostic criterion for the outcome of Stage I renal cell carcinoma.
              Article 0 comments Cited 470 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Xiaohan Qu: han_seal@163.com
                Jinlu Liu: lnljl520@126.com
                Xinwen Zhong: xwzhong@mail.cmu.edu.cn
                Xi Li: 13889853625@163.com
                Qigang Zhang: 18040097645@163.com
                Journal
                Journal ID (nlm-ta): J Transl Med
                Journal ID (iso-abbrev): J Transl Med
                Title: Journal of Translational Medicine
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1479-5876
                Publication date (Electronic): 15 September 2015
                Publication date PMC-release: 15 September 2015
                Publication date Collection: 2015
                Volume: 13
                Electronic Location Identifier: 301
                Affiliations
                [ ]The First Affiliated Hospital, China Medical University, NO. 155, Nanjing North Street, Heping District, Shenyang, 110001 Liaoning China
                [ ]The Forth Affiliated Hospital, China Medical University, Shenyang, China
                Article
                Publisher ID: 666
                DOI: 10.1186/s12967-015-0666-y
                PMC ID: 4571108
                PubMed ID: 25591711
                SO-VID: 7502696f-4a7a-45bb-ad5c-e3e227715d72
                Copyright © © Qu et al. 2015
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 28 April 2015
                Date accepted : 9 September 2015
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2015

                ScienceOpen disciplines: Medicine
                Keywords: piwil2,non-small cell lung cancer,cyclin a,cdk2,prognosis
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: piwil2, non-small cell lung cancer, cyclin a, cdk2, prognosis

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