Dataset Information

Integrative analysis reveals driver long non-coding RNAs in osteosarcoma.

ABSTRACT: Transcriptome profiling of osteosarcoma (OS) by next generation sequencing technology (NGS) has been broadly performed by previous researches, which uncovers a large number protein-coding driver genes, facilitates our understanding of the molecular mechanisms of OS formation, progression and metastasis. Recently, more and more researchers realize the importance of long non-coding RNAs (lncRNAs) on the development of OS. However, few studies focus on discovering driver lncRNAs.Here we collected somatic copy number alterations (SCNAs) and gene expression profiles of 84 samples from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) project. The RNA sequencing data detected 13,903 expressed lncRNAs, 157 of which were previously reported to be associated with cancer based on the annotations from Lnc2Cancer database.By analyzing the SNP array data, several significant SCNAs were detected, such as the amplifications on chromosomes 1q, 4q, 17p, 17q, and 19q, and deletions on 1q, 3q, 9p, 10q, and 15q. With the SCNA and gene expression profiles, we identified 167 driver genes by integrative analysis, including 162 novel driver lncRNAs, 2 lncRNAs reported to be associated with OS, and another 3 associated with other cancers. Furthermore, functional characterization and survival analysis revealed that RP11-241F15.10 may function as a tumor suppressor in OS, and loss of function may contribute to activation of Wnt signaling pathway.This study not only facilitates our understanding of the oncogenic or tumor-suppressor role of lncRNAs in OS, but also provides potential therapies for the patients with OS with metastasis or relapse.

SUBMITTER: Luo Z

PROVIDER: S-EPMC6380806 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Integrative analysis reveals driver long non-coding RNAs in osteosarcoma.

Luo Zhenguo Z Xiao Li L Li Jing J Dong Buhuai B Wang Chunsheng C

Medicine 20190201 6

Transcriptome profiling of osteosarcoma (OS) by next generation sequencing technology (NGS) has been broadly performed by previous researches, which uncovers a large number protein-coding driver genes, facilitates our understanding of the molecular mechanisms of OS formation, progression and metastasis. Recently, more and more researchers realize the importance of long non-coding RNAs (lncRNAs) on the development of OS. However, few studies focus on discovering driver lncRNAs.Here we collected s ...[more]

PMID: 30732148

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Project description:Recently, large numbers of normal human tissues have been profiled for non-coding RNAs and more than fourteen thousand long intergenic non-coding RNAs (lincRNAs) are found expressed in normal human tissues. The functional roles of these normal lincRNAs (nlincRNAs) in the regulation of protein coding genes in normal and disease biology are yet to be established. Here, we have profiled two RNA-seq datasets including cancer and matched non-neoplastic tissues from 12 individuals from diverse demography for both coding genes and nlincRNAs. We find 130 nlincRNAs significantly regulated in cancer, with 127 regulated in the same direction in the two datasets. Interestingly, according to Illumina Body Map, significant numbers of these nlincRNAs display baseline null expression in normal prostate tissues but are specific to other tissues such as thyroid, kidney, liver and testis. A number of the regulated nlincRNAs share loci with coding genes, which are either co-regulated or oppositely regulated in all cancer samples studied here. For example, in all cancer samples i) the nlincRNA, TCONS_00029157, and a neighboring tumor suppressor factor, SIK1, are both down regulated; ii) several thyroid-specific nlincRNAs in the neighborhood of the thyroid-specific gene TPO, are both up-regulated; and iii) the TCONS_00010581, an isoform of HEIH, is down-regulated while the neighboring EZH2 gene is up-regulated in cancer. Several nlincRNAs from a prostate cancer associated chromosomal locus, 8q24, are up-regulated in cancer along with other known prostate cancer associated genes including PCAT-1, PVT1, and PCAT-92. We observe that there is significant bias towards up-regulation of nlincRNAs with as high as 118 out of 127 up-regulated in cancer, even though regulation of coding genes is skewed towards down-regulation. Considering that all reported cancer associated lincRNAs (clincRNAs) are biased towards up-regulation, we conclude that this bias may be functionally relevant.

Dataset Information

Integrative analysis reveals driver long non-coding RNAs in osteosarcoma.

Publications

Integrative analysis reveals driver long non-coding RNAs in osteosarcoma.

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