Abstract
Sarcoma includes some of the most heterogeneous tumors, which make the diagnosis, prognosis and treatment of these rare yet diverse neoplasms especially challenging. Long noncoding RNAs (lncRNAs) are important regulators of cancer initiation and progression, which implies their potential as neoteric prognostic and diagnostic markers in cancer, including sarcoma. A relationship between lncRNAs and sarcoma pathogenesis and progression is emerging. Recent studies demonstrate that lncRNAs influence sarcoma cell proliferation, metastasis, and drug resistance. Additionally, lncRNA expression profiles are predictive of sarcoma prognosis. In this review, we summarize contemporary advances in the research of lncRNA biogenesis and functions in sarcoma. We also highlight the potential for lncRNAs to become innovative diagnostic and prognostic biomarkers as well as therapeutic targets in sarcoma.
Highlights
Sarcoma is a heterogeneous group with more than 70 malignant primary neoplasms of mesenchymal origin [1,2]
In blood samples of osteosarcoma patients, taurine upregulated gene 1 (TUG1) expression levels were decreased in postoperative patients in comparison with preoperative patients, and the changes of TUG1 expression were significantly associated with disease status [78]
With the development of advanced molecular biological techniques— microarray and high-throughput screening—growing evidence demonstrates that Long noncoding RNAs (lncRNAs) are involved in sarcomas, namely osteosarocma, Ewing’s sarcoma and gastrointestinal stromal tumors (GISTs)
Summary
Sarcoma is a heterogeneous group with more than 70 malignant primary neoplasms of mesenchymal origin [1,2]. Other lncRNAs affect osteosarcoma cell proliferation by interacting with miRNAs and lncRNAs. The expression levels of taurine upregulated gene 1 (TUG1) were significantly higher in human osteosarcoma tissue compared with matched non-tumorous tissue [55]. ZEB1-AS1 Zinc Finger E-Box Binding Homeobox 1 Antisense RNA 1 (ZEB1-AS1) expression was upregulated in human osteosarcoma tissue and cell lines [74]. ZEB1-AS1 directly binds and recruits p300 to the ZEB1 promoter region, induces an open chromatin structure, and activates ZEB1 transcription [74] This mechanism related to ZEB1-AS1 knockdown suggests a significant correlation between the expression of ZEB1-AS1 and ZEB1 in human osteosarcoma tissue [74]. LncRNAs can influence osteosarcoma cell proliferation by other mechanisms, such as controlling gene expression. The inhibition of HOTAIR downregulated the transforming growth factor-β (TGF-β) and Bcl-2, and upregulated p53 and the tumor necrosis factor-α (TNF-α) [61] (Table 1)
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