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      LINC00514 drives osteosarcoma progression through sponging microRNA-708 and consequently increases URGCP expression

      research-article
      1 , 2 , 3 , 4 ,
      Aging (Albany NY)
      Impact Journals
      long noncoding RNA, osteosarcoma, microRNA

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          Abstract

          Long intergenic nonprotein-coding RNA 00514 (LINC00514) is upregulated in papillary thyroid cancer and contributes to its aggressiveness. In this study, we thoroughly explored the expression profile, specific functions, and relevant molecular mechanism of LINC00514 in osteosarcoma (OS). Herein, LINC00514 was significantly upregulated in OS tissues and cells, and increased LINC00514 expression was closely correlated with tumor size, TNM stage, and distant metastasis. OS patients with high LINC00514 expression had shorter overall survival than those with low LINC00514 expression. LINC00514 interference inhibited OS cell proliferation, colony formation, migration, and invasion in vitro but promoted cell apoptosis and G0/G1 cell cycle arrest. LINC00514 downregulation hindered OS tumor growth in vivo. Mechanistically, LINC00514 functioned as a competing endogenous RNA by directly interacting with microRNA-708-5p (miR-708) and consequently increasing the expression of upregulator of cell proliferation (URGCP). Both miR-708 knockdown and URGCP restoration partially neutralized anticancer activities of LINC00514 silencing in OS cells. LINC00514 increases URGCP expression by acting as a competing endogenous RNA for miR-708, thus exerting oncogenic roles in OS progression. In conclusion, the LINC00514/miR-708/URGCP pathway may be a promising target for drug discovery in the future.

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          Most cited references33

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          The bright side of dark matter: lncRNAs in cancer.

          The traditional view of genome organization has been upended in the last decade with the discovery of vast amounts of non-protein-coding transcription. After initial concerns that this "dark matter" of the genome was transcriptional noise, it is apparent that a subset of these noncoding RNAs are functional. Long noncoding RNA (lncRNA) genes resemble protein-coding genes in several key aspects, and they have myriad molecular functions across many cellular pathways and processes, including oncogenic signaling. The number of lncRNA genes has recently been greatly expanded by our group to triple the number of protein-coding genes; therefore, lncRNAs are likely to play a role in many biological processes. Based on their large number and expression specificity in a variety of cancers, lncRNAs are likely to serve as the basis for many clinical applications in oncology.
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            Osteosarcoma Overview

            Osteosarcoma (OS) is the most common primary malignancy of bone and patients with metastatic disease or recurrences continue to have very poor outcomes. Unfortunately, little prognostic improvement has been generated from the last 20 years of research and a new perspective is warranted. OS is extremely heterogeneous in both its origins and manifestations. Although multiple associations have been made between the development of osteosarcoma and race, gender, age, various genomic alterations, and exposure situations among others, the etiology remains unclear and controversial. Noninvasive diagnostic methods include serum markers like alkaline phosphatase and a growing variety of imaging techniques including X-ray, computed tomography, magnetic resonance imaging, and positron emission as well as combinations thereof. Still, biopsy and microscopic examination are required to confirm the diagnosis and carry additional prognostic implications such as subtype classification and histological response to neoadjuvant chemotherapy. The current standard of care combines surgical and chemotherapeutic techniques, with a multitude of experimental biologics and small molecules currently in development and some in clinical trial phases. In this review, in addition to summarizing the current understanding of OS etiology, diagnostic methods, and the current standard of care, our group describes various experimental therapeutics and provides evidence to encourage a potential paradigm shift toward the introduction of immunomodulation, which may offer a more comprehensive approach to battling cancer pleomorphism.
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              Osteosarcoma, chondrosarcoma, and Ewing's sarcoma: National Cancer Data Base Report.

              We summarize descriptive epidemiologic and survival data from the National Cancer Data Base of the American College of Surgeons for 26,437 cases of osteosarcoma (n = 11,961), chondrosarcoma (n = 9606), and Ewing's sarcoma (n = 4870) from 1985 to 2003. Survival data are reported on cases with a minimum 5-year followup from 1985 to 1998 (8,104 osteosarcomas, 6,476 chondrosarcomas, and 3,225 Ewing's sarcomas). The relative 5-year survival rate was 53.9% for osteosarcoma, 75.2% for chondrosarcoma, and 50.6% for Ewing's sarcoma. Survival rates did not change notably over the collection period. Within osteosarcomas, the relative 5-year survival rates were 52.6% for high grade, 85.9% for parosteal, and 17.8% for Paget's subtypes. For osteosarcoma patients, the relative 5-year survival rate was 60% for those younger than 30 years, 50% for those aged 30 to 49 years, and 30% for those aged 50 years or older. Within chondrosarcomas, the relative 5-year survival rate was 76% for conventional, 71% for myxoid, 87% for juxtacortical, and 52% for mesenchymal. While the National Cancer Data Base has limitations, the survival data and demographics for bone sarcomas are unprecedented in numbers and duration. Our report supports continued efforts to refine data collection and stimulate further data analysis.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                30 April 2020
                23 April 2020
                : 12
                : 8
                : 6793-6807
                Affiliations
                [1 ]Department of Spine Surgery, Shandong Provincial ENT Hospital, Shandong Provincial ENT Hospital Affiliated to Shandong University, Ji’nan 250022, Shandong, China
                [2 ]Department of Traumatic Orthopedics, Shandong Provincial ENT Hospital, Shandong Provincial ENT Hospital Affiliated to Shandong University, Ji’nan 250022, Shandong, China
                [3 ]Orthopedic and Soft Tissue Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji’nan 250117, Shandong, China
                [4 ]Department of Orthopedics, Shandong Provincial Third Hospital, Ji’nan 250031, Shandong, China
                Author notes
                [*]

                Co-first authors

                Correspondence to: Kai Zhang; email: zhangkai_spth@163.com
                Article
                103043 103043
                10.18632/aging.103043
                7202513
                32325430
                bc34bca4-e6be-4cc8-bbbb-2ef2a15b950b
                Copyright © 2020 Yu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 03 February 2020
                : 17 March 2020
                Categories
                Research Paper

                Cell biology
                long noncoding rna,osteosarcoma,microrna
                Cell biology
                long noncoding rna, osteosarcoma, microrna

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