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      The lncRNA PCAT1 is correlated with poor prognosis and promotes cell proliferation, invasion, migration and EMT in osteosarcoma

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          Abstract

          Introduction

          Osteosarcoma is a malignant primary bone cancer and is lethal to children and adolescents. Recently, the dysregulation of long noncoding RNAs (lncRNAs) has been shown in various types of cancers.

          Aim

          The present study aimed to examine the role of the lncRNA prostate cancer-associated transcript 1 (PCAT1) in osteosarcoma progression.

          Materials and methods

          The expression levels of relevant genes in clinical samples and cell lines were determined by quantitative real-time polymerase chain reaction. Cell proliferation, invasion and migration were examined by CCK-8 assay, transwell invasion and migration assay, respectively. Cell apoptosis and cell cycle were detected by flow cytometry. Protein levels were detected by Western blot.

          Results

          Our results showed that PCAT1 was upregulated in osteosarcoma tissues when compared to normal bone tissues. PCAT1 was also upregulated in osteosarcoma cell lines when compared to normal bone cell line. The upregulation of PCAT1 was significantly associated with advanced clinical stage, tumor metastasis and shorter overall survival in patients with osteosarcoma. In vitro studies showed that overexpression of PCAT1 in MG-63 cells enhanced cell proliferation, cell invasion and migration and epithelial-to-mesenchymal transition (EMT); decreased cell apoptotic rate; and also caused an increase in cell population at S phase with a decrease in cell population at G 0/G 1 phase. Knockdown of PCAT1 in U2OS cells suppressed cell proliferation, cell invasion and migration, and EMT; increased cell apoptotic rate; and caused an increase in the cell population at G 0/G 1 phase with a decrease in cell population at S phase.

          Conclusion

          Taken together, our results suggest the oncogenic role of PCAT1 in osteosarcoma progression.

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          Most cited references 23

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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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            Overexpression of long noncoding RNA PCAT-1 is a novel biomarker of poor prognosis in patients with colorectal cancer.

            Long noncoding RNAs (lncRNA) are emerging as key molecules in human cancer. Prostate cancer-associated ncRNA transcripts 1 (PCAT-1), a lncRNA, has been recently revealed involving in human prostate cancer progression. However, whether PCAT-1 could serve as novel biomarker to predict prognosis in colorectal cancer (CRC) or not is unknown. We therefore carried out the present study to explore the correlation between PCAT-1 expression and the progression of CRC. In this study, the expression of PCAT-1 in 108 cases of CRC tissues and matched 81 adjacent normal tissues were determined by quantitative real-time PCR. Furthermore, the copy number variation of PCAT-1 was also measured in 17 tumor tissues and matched normal tissues. Our results showed that PCAT-1 expression in CRC tissues was significantly upregulated compared with the matched normal tissues (p < 0.001) and the overexpression of PCAT-1(upregulated by more than 50 %) was found in 64 % (62/81) of CRC. Moreover, PCAT-1 gene copy number variation explains only a few percent of observed overexpression. In addition, there was a significant association between PCAT-1 expression and distant metastasis (p = 0.04), but not other clinical characteristics. More important, CRC patients with PCAT-1 higher expression have shown significantly poorer overall survival than those with lower PCAT-1 expression (p < 0.001). Also, multivariable Cox regression analysis identified PCAT-1 overexpression as an independent prognostic factor for CRC (p = 0.007, HR = 3.12 95 %CI = 1.355-7.185). In conclusion, our results suggest that high expression of PCAT-1 is involved in CRC progression and could be a novel biomarker of poor prognosis in patient with colorectal cancer.
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              EMT transcription factors: implication in osteosarcoma.

              The primary malignant bone tumor, osteosarcoma, is a deadly disorder. Its etiology is complex, and treatment is mostly obscure. The transcription factors (TFs) involved in epithelial to mesenchymal transition (EMT) have significant role in osteosarcoma. A number of evidence suggests that overexpression of EMT-TFs, such as Twist, Snails and Zebs, is involved in complex pathogenesis of osteosarcoma. Recent research studies have showed some extent of promise in osteosarcoma treatment by targeting these EMT-TFs. However, success in research on osteosarcoma-EMT-TFs axis is just in primary stage, and a long way to go. Targeting Twist, Snail or Zeb by specific molecules or chemotherapeutic agents may provide a new dimension in osteosarcoma treatment by controlling metastasis.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2018
                31 January 2018
                : 11
                : 629-638
                Affiliations
                [1 ]Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin
                [2 ]Department of Orthopedics, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China
                Author notes
                Correspondence: Xinlong Ma, Department of Orthopedics, Tianjin Medical University General Hospital, No 122, Munan Road, Heping District, Tianjin 300052, People’s Republic of China, Tel +86 137 1898 1077, Email mxlvic@ 123456126.com
                Article
                ott-11-629
                10.2147/OTT.S152063
                5797453
                © 2018 Zhang et al. 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.

                Categories
                Original Research

                Oncology & Radiotherapy

                osteosarcoma, pcat1, metastasis, overall survival, cell proliferation, emt

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