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      GAPLINC is a predictor of poor prognosis and regulates cell migration and invasion in osteosarcoma

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          Abstract

          Gastric adenocarcinoma predictive long intergenic non-coding (GAPLINC) is a novel long non-coding RNA (lncRNA) and has been found to function as an oncogenic lncRNA in gastric cancer, colorectal cancer, and bladder cancer. The expression status and biological function of GAPLINC in osteosarcoma are still unknown. Thus, we analyzed the association between GAPLINC expression and clinicopathological characteristics in osteosarcoma clinical samples, and conducted loss-of-function study in osteosarcoma cell lines. In our results, GAPLINC expression is elevated in osteosarcoma tissues and cell lines, and correlated with advanced Enneking stage, present distant metastasis, and poor histological grade. Survival analyses indicated that GAPLINC expression was negatively associated with overall survival, and GAPLINC high-expression was an independent risk factor in osteosarcoma patients. The in vitro studies showed knockdown of GAPLINC depressed osteosarcoma cell migration and invasion via inhibiting CD44 expression, but no effect on cell proliferation. In conclusion, GAPLINC may serve as a potential biomarker for predicting prognosis and developing therapy for osteosarcoma.

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          Long noncoding RNA GAPLINC regulates CD44-dependent cell invasiveness and associates with poor prognosis of gastric cancer.

          Yingxuan Chen, Haoyan Chen, Jilin Wang … (2014)
          It is increasingly evident that long noncoding RNAs (lncRNA) have causative roles in carcinogenesis. In this study, we report findings implicating a novel lncRNA in gastric cancer, termed GAPLINC (gastric adenocarcinoma predictive long intergenic noncoding RNA), based on the use of global microarray and in situ hybridization (ISH) analyses to identify aberrantly expressed lncRNA in human gastric cancer specimens. GAPLINC is a 924-bp-long lncRNA that is highly expressed in gastric cancer tissues. GAPLINC suppression and with gene expression profiling in gastric cancer cells revealed alterations in cell migration pathways, with CD44 expression the most highly correlated. Manipulating GAPLINC expression altered CD44 mRNA abundance and the effects of GAPLINC on cell migration and proliferation were neutralized by suppressing CD44 expression. Mechanistic investigations revealed that GAPLINC regulates CD44 as a molecular decoy for miR211-3p, a microRNA that targets both CD44 and GAPLINC. Tissue ISH analysis suggested that GAPLINC overexpression defines a subgroup of patients with gastric cancer with very poor survival. Taken together, our results identify a noncoding regulatory pathway for the CD44 oncogene, shedding new light on the basis for gastric cancer cell invasiveness. ©2014 American Association for Cancer Research.
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            Long Non-Coding RNA ucoo2kmd.1 Regulates CD44-Dependent Cell Growth by Competing for miR-211-3p in Colorectal Cancer

            Xiaoli Wu, Xixi He, Fang-Shi Li … (2016)
            In addition to protein-coding genes, the human genome makes a large amount of noncoding RNAs. Long non-coding RNAs (lncRNAs) have been described as the largest subclass of the non-coding transcriptome in human noncoding RNAs. In recent years, lncRNAs have been considered to be the key regulators of tumor behavior. In this study, based on previous research, we investigated the expression and biological role of a newly identified cancer-related lncRNA, lncRNA-uc002kmd.1. We analyzed the relationship between lncRNA-uc002kmd.1 and colorectal cancer (CRC) in a total 45 CRC and paired adjacent, non-tumor tissue samples. We found that lncRNA-uc002kmd.1 expression was usually highly expressed in carcinoma compared with the tissue adjacent to the carcinoma. Through a series of experiments, the results showed that lncRNA-uc002kmd.1 regulates CD44 as a molecular decoy for miR211-3p. Our data indicated that the overexpression of lncRNA-uc002kmd.1 enhanced cell proliferation in CRC.
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              Long noncoding RNA GAPLINC promotes invasion in colorectal cancer by targeting SNAI2 through binding with PSF and NONO

              Peng Yang, Tao Chen, Zipeng Xu … (2016)
              This study aimed to investigate the role of long noncoding RNAs (lncRNAs) in the metastasis of colorectal cancer (CRC). Metastasis is an important prognostic factor of CRC, and lncRNAs have been implicated in tumor proliferation and metastasis. The human CRC cell lines HCT116, HT29, SW480, DLD-1, and SW620 were used in the study. Genome-wide lncRNA expression patterns in metastatic lymph nodes compared with paired normal lymph nodes of CRC were assessed by microarray analysis. Gastric adenocarcinoma predictive long intergenic noncoding (GAPLINC) RNA was detected via functional prediction. The increased expression of GAPLINC was found to be positively correlated with larger tumor size, advanced tumor stage (T stage), advanced node stage (N stage), increased death, and shorter survival of patients with CRC by in situ hybridization analysis. Besides, the decreased expression of GAPLINC could significantly repress CRC cell invasion in vitro and also inhibit proliferation in vitro and in vivo. RNA pull-down with mass spectrum experiments revealed that PTB-associated splicing factor (PSF) and non-POU-domain-containing octamer-binding (NONO) protein bound to GAPLINC and reversed the effect of GAPLINC on cell invasion. Gene array and bioinformatics analyses identified that snail family zinc finger 2 (SNAI2) was involved in the biological processes of GAPLINC/PSF/NONO. This study indicated the importance of GAPLINC in promoting CRC invasion via binding to PSF/NONO and partly by stimulating the expression of SNAI2. Hence, GAPLINC may serve as a promising target for CRC diagnosis and therapy. The findings may help in developing a novel therapeutic strategy for patients with CRC.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biosci Rep
                Journal ID (iso-abbrev): Biosci. Rep
                Journal ID (hwp): ppbioscirep
                Journal ID (publisher-id): BSR
                Title: Bioscience Reports
                Publisher: Portland Press Ltd.
                ISSN (Print): 0144-8463
                ISSN (Electronic): 1573-4935
                Publication date (Electronic preprint): 31 August 2018
                Publication date Collection: 31 October 2018
                Publication date (Electronic): 10 October 2018
                Volume: 38
                Issue: 5
                Electronic Location Identifier: BSR20181171
                Affiliations
                [1 ]Department of Bone and Soft Tissue Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
                [2 ]Department of Orthopedics, First Central Clinical College, Tianjin Medical University, Nankai District 300110, Tianjin, China
                [3 ]Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
                Author notes
                Correspondence: Chao Wang ( wangchaodr135@ 123456sina.com )
                [*]

                These authors contributed equally to this work.

                Article
                DOI: 10.1042/BSR20181171
                PMC ID: 6177557
                PubMed ID: 30177521
                SO-VID: b6793e7a-3a78-4372-80e2-e94e45d2e47a
                Copyright © © 2018 The Author(s).
                License:

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                Date received : 15 July 2018
                Date revision received : 18 August 2018
                Date accepted : 23 August 2018
                Page count
                Pages: 8
                Categories
                Subject: Research Articles
                Subject: Research Article
                Subject: 25
                Subject: 16

                ScienceOpen disciplines: Life sciences
                Keywords: biomarker,gaplinc,large intervening non-coding rna,osteosarcoma
                Data availability:
                ScienceOpen disciplines: Life sciences
                Keywords: biomarker, gaplinc, large intervening non-coding rna, osteosarcoma

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