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      A Probabilistic Matrix Factorization Method for Identifying lncRNA-Disease Associations

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          Abstract

          Recently, an increasing number of studies have indicated that long-non-coding RNAs (lncRNAs) can participate in various crucial biological processes and can also be used as the most promising biomarkers for the treatment of certain diseases such as coronary artery disease and various cancers. Due to costs and time complexity, the number of possible disease-related lncRNAs that can be verified by traditional biological experiments is very limited. Therefore, in recent years, it has been very popular to use computational models to predict potential disease-lncRNA associations. In this study, we constructed three kinds of association networks, namely the lncRNA-miRNA association network, the miRNA-disease association network, and the lncRNA-disease correlation network firstly. Then, through integrating these three newly constructed association networks, we constructed an lncRNA-disease weighted association network, which would be further updated by adopting the KNN algorithm based on the semantic similarity of diseases and the similarity of lncRNA functions. Thereafter, according to the updated lncRNA-disease weighted association network, a novel computational model called PMFILDA was proposed to infer potential lncRNA-disease associations based on the probability matrix decomposition. Finally, to evaluate the superiority of the new prediction model PMFILDA, we performed Leave One Out Cross-Validation (LOOCV) based on strongly validated data filtered from MNDR and the simulation results indicated that the performance of PMFILDA was better than some state-of-the-art methods. Moreover, case studies of breast cancer, lung cancer, and colorectal cancer were implemented to further estimate the performance of PMFILDA, and simulation results illustrated that PMFILDA could achieve satisfying prediction performance as well.

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          Most cited references37

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          Long non-coding RNAs and complex diseases: from experimental results to computational models

          Abstract LncRNAs have attracted lots of attentions from researchers worldwide in recent decades. With the rapid advances in both experimental technology and computational prediction algorithm, thousands of lncRNA have been identified in eukaryotic organisms ranging from nematodes to humans in the past few years. More and more research evidences have indicated that lncRNAs are involved in almost the whole life cycle of cells through different mechanisms and play important roles in many critical biological processes. Therefore, it is not surprising that the mutations and dysregulations of lncRNAs would contribute to the development of various human complex diseases. In this review, we first made a brief introduction about the functions of lncRNAs, five important lncRNA-related diseases, five critical disease-related lncRNAs and some important publicly available lncRNA-related databases about sequence, expression, function, etc. Nowadays, only a limited number of lncRNAs have been experimentally reported to be related to human diseases. Therefore, analyzing available lncRNA–disease associations and predicting potential human lncRNA–disease associations have become important tasks of bioinformatics, which would benefit human complex diseases mechanism understanding at lncRNA level, disease biomarker detection and disease diagnosis, treatment, prognosis and prevention. Furthermore, we introduced some state-of-the-art computational models, which could be effectively used to identify disease-related lncRNAs on a large scale and select the most promising disease-related lncRNAs for experimental validation. We also analyzed the limitations of these models and discussed the future directions of developing computational models for lncRNA research.
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            DD3: a new prostate-specific gene, highly overexpressed in prostate cancer.

            Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in the Western male population. Despite the tremendous efforts that have been made to improve the early detection of this disease and to design new treatment modalities, there is still an urgent need for new markers and therapeutic targets for the management of prostate cancer patients. Using differential display analysis to compare the mRNA expression patterns of normal versus tumor tissue of the human prostate, we identified a cDNA, DD3, which is highly overexpressed in 53 of 56 prostatic tumors in comparison to nonneoplastic prostatic tissue of the same patients. Reverse transcription-PCR analysis using DD3-specific primers indicated that the expression of DD3 is very prostate specific because no product could be amplified in 18 different normal human tissues studied. Also, in a sampling of other tumor types and a large number of cell lines, no expression of DD3 could be detected. Molecular characterization of the DD3 transcription unit revealed that alternative splicing and alternative polyadenylation occur. The fact that no extensive open reading frame could be found suggests that DD3 may function as a noncoding RNA. The DD3 gene was mapped to chromosome 9q21-22, and no homology of DD3 to any gene present in the computer databases was found. Our data indicate that DD3 is one of the most prostate cancer-specific genes yet described, and this makes DD3 a promising marker for the early diagnosis of prostate cancer and provides a powerful tool for the development of new treatment strategies for prostate cancer patients.
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              Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex

              Background: Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) is a functional long non-coding RNA (lncRNA), which is highly expressed in several tumours, including colorectal cancer (CRC). Its biological function and mechanism in the prognosis of human CRC is still largely under investigation. Methods: This study aimed to investigate the new effect mechanism of MALAT1 on the proliferation and migration of CRC cells in vitro and in vivo, and detect the expression of MALAT1, SFPQ (also known as PSF (PTB-associated splicing factor)), and PTBP2 (also known as PTB (polypyrimidine-tract-binding protein)) in CRC tumour tissues, followed by correlated analysis with clinicopathological parameters. Results: We found that overexpression of MALAT1 could promote cell proliferation and migration in vitro, and promote tumour growth and metastasis in nude mice. The underlying mechanism was associated with tumour suppressor gene SFPQ and proto-oncogene PTBP2. In CRC, MALAT1 could bind to SFPQ, thus releasing PTBP2 from the SFPQ/PTBP2 complex. In turn, the increased SFPQ-detached PTBP2 promoted cell proliferation and migration. SFPQ critically mediated the regulatory effects of MALAT1. Moreover, in CRC tissues, MALAT1 and PTBP2 were overexpressed, both of which were associated closely with the invasion and metastasis of CRC. However, the SFPQ showed unchanged expression either in CRC tissues or adjacent normal tissues. Conclusions: Our findings implied that MALAT1 might be a potential predictor for tumour metastasis and prognosis. Furthermore, the interaction between MALAT1 and SFPQ could be a novel therapeutic target for CRC.
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                Author and article information

                Journal
                Genes (Basel)
                Genes (Basel)
                genes
                Genes
                MDPI
                2073-4425
                08 February 2019
                February 2019
                : 10
                : 2
                : 126
                Affiliations
                [1 ]College of Computer Engineering & Applied Mathematics, Changsha University, Changsha 410001, China; Zhanwei_xuan@ 123456163.com (Z.X.); lijiechen39555@ 123456163.com (J.L.); jingwen.yu18@ 123456gmail.com (J.Y.); fengxiang@ 123456xtu.edu.cn (X.F.); bihaizhao@ 123456163.com (B.Z.)
                [2 ]Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan 411105, China
                Author notes
                [* ]Correspondence: wanglei@ 123456xtu.edu.cn ; Tel.: +86-151-1110-9999
                Author information
                https://orcid.org/0000-0002-1599-2191
                https://orcid.org/0000-0002-5065-8447
                Article
                genes-10-00126
                10.3390/genes10020126
                6410097
                30744078
                f55ea3d8-301d-44d1-9608-91369af7f360
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 December 2018
                : 04 February 2019
                Categories
                Article

                lncrna,disease,mirna,lncrna-disease associations,identifying disease-related lncrna

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