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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p

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          Abstract

          Objective

          Cervical cancer is one of the most common female malignancies worldwide and represents a major global health challenge. The fast growth of tumor and high rates of metastasis still lead to a poor prognosis of cervical cancer patients. It is urgent to clarify the mechanism and identify predictive biomarkers for the treatment of cervical cancer. Long non-coding RNAs (LncRNAs) have been identified in cervical cancer and are related to malignant phenotypes of cervical cancer cells. However, the roles and mechanism of LncRNA deleted in lymphocytic leukemia (DLEU2) in the tumorigenesis and progression of cervical cancer remain unknown.

          Materials and Methods

          qPCR was performed to analyze the expression of DLEU2, Cyclin D1, CDK4, Bax, Bcl2 and mi-128-3p. Western blot was performed to detect the cell cycle hallmarks expression. CCK8 was used to examine cell proliferation. Cellular apoptosis was analyzed by Hoechst 33,258 staining and AV/PI staining with flow cytometry. Cell cycle was analyzed by flow cytometry. The xenograft model in nude mice was used to elucidate the function of DLEU2 in vivo. Bioinformatics analysis and luciferase reporter assay were proceeded to clarify whether miR-128-3p directly binds with lncRNA DLEU2. Pull‑down assay and RNA-binding protein immunoprecipitation assay were used for exploring the relationship between DLEU2 and miR-128-3p.

          Results

          We demonstrated that DLEU2 was upregulated in cervical cancer tumor tissues. Downregulation of DLEU2 inhibited cell proliferation, induced apoptosis and cell cycle arrest at G2/M phase of cervical cancer cells in vitro, and suppressed tumor growth in vivo. Further, LncRNA DLEU2 is one of the targets of miR-128-3p. miR-128-3p inhibitor abrogated the cell proliferation suppressed by knockdown of DLEU2, apoptosis induced by knockdown of DLEU2 and reversed the expression of cell cycle hallmarks regulated by knockdown of DLEU2.

          Conclusion

          Taken together, these results suggested knockdown of DLEU2 inhibited cervical cancer progression via targeting miR-128-3p.

          Most cited references53

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Long non-coding RNAs: insights into functions.

            Tim Mercer, Marcel E Dinger, John S. Mattick (2009)
            In mammals and other eukaryotes most of the genome is transcribed in a developmentally regulated manner to produce large numbers of long non-coding RNAs (ncRNAs). Here we review the rapidly advancing field of long ncRNAs, describing their conservation, their organization in the genome and their roles in gene regulation. We also consider the medical implications, and the emerging recognition that any transcript, regardless of coding potential, can have an intrinsic function as an RNA.
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              Cervical cancer

              Paul A. Cohen, Anjua Jhingran, Ana Oaknin … (2019)
              Each year, more than half a million women are diagnosed with cervical cancer and the disease results in over 300 000 deaths worldwide. High-risk subtypes of the human papilloma virus (HPV) are the cause of the disease in most cases. The disease is largely preventable. Approximately 90% of cervical cancers occur in low-income and middle-income countries that lack organised screening and HPV vaccination programmes. In high-income countries, cervical cancer incidence and mortality have more than halved over the past 30 years since the introduction of formal screening programmes. Treatment depends on disease extent at diagnosis and locally available resources, and might involve radical hysterectomy or chemoradiation, or a combination of both. Conservative, fertility-preserving surgical procedures have become standard of care for women with low-risk, early-stage disease. Advances in radiotherapy technology, such as intensity-modulated radiotherapy, have resulted in less treatment-related toxicity for women with locally-advanced disease. For women with metastatic or recurrent disease, the overall prognosis remains poor; nevertheless, the incorporation of the anti-VEGF agent bevacizumab has been able to extend overall survival beyond 12 months. Preliminary results of novel immunotherapeutic approaches, similarly to other solid tumours, have shown promising results so far.
              Article 0 comments Cited 776 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): ott
                Journal ID (pmc): ott
                Title: OncoTargets and therapy
                Publisher: Dove
                ISSN (Electronic): 1178-6930
                Publication date (Electronic): 09 October 2020
                Publication date Collection: 2020
                Volume: 13
                Pages: 10173-10184
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Weifang NO.2 People’s Hospital
                [2 ]Center for Reproductive Medicine , Department of Obstetrics and Gynecology, Beijing, People’s Republic of China
                [3 ]Peking University Third Hospital , Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, People’s Republic of China
                [4 ]Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction , Beijing, People’s Republic of China
                [5 ]Department of Obstetrics and Gynecology, Affiliated Yixing Hospital of Jiangsu University , Jiangsu, People’s Republic of China
                [6 ]Department of Orthopedics, Peking University Third Hospital , Beijing, People’s Republic of China
                [7 ]Beijing Key Laboratory of Spinal Disease , Beijing, People’s Republic of China
                Author notes
                Correspondence: Weiling Li Department of Obstetrics and Gynecology, Affiliated Yixing Hospital of Jiangsu University , No. 75. Tongzhenguan Road, Yixing, People’s Republic of ChinaTel +86-13921327907 Email liweiling_1989@163.com
                Wanqiong Yuan Department of Orthopedics Peking University Third Hospital , 49 North Garden Road, Haidian District, Beijing, People’s Republic of ChinaTel +86-15120092324Fax +86 10-82266611 Email yuanwanqiong@126.com
                Author information
                http://orcid.org/0000-0002-0334-6467
                Article
                Publisher ID: 272292
                DOI: 10.2147/OTT.S272292
                PMC ID: 7553767
                PubMed ID: 33116599
                SO-VID: fa804028-b925-4288-bbcb-1caf05d7b541
                Copyright © © 2020 Wang et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 15 July 2020
                Date accepted : 11 September 2020
                Page count
                Figures: 5, Tables: 2, References: 53, Pages: 12
                Funding
                Funded by: the National Key R&D Program of China;
                Funded by: the Key Clinical Projects of Peking University Third Hospital;
                This work was supported by the National Key R&D Program of China (Grant Nos. 2018YFC1003702, 2018YFC1004403) and the Key Clinical Projects of Peking University Third Hospital (Grant No. BYSYZD2019041).
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cervical cancer,lncrnas,dleu2,mir-128-3p,tumor growth
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cervical cancer, lncrnas, dleu2, mir-128-3p, tumor growth

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