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Abstract：
BACKGROUND: Long noncoding RNAs (lncRNAs) are noncoding RNA transcripts greater than 200 nucleotides in length and are known to play a role in regulating the transcription of genes involved in vital cellular functions. We hypothesized the disease process in dysferlinopathy is linked to an aberrant expression of lncRNAs and messenger RNAs (mRNAs).
OBJECTIVE: In this study, we compared the lncRNA and mRNA expression profiles between wild-type and dysferlin-deficient murine myoblasts (C2C12 cells).
METHODS: LncRNA and mRNA expression profiling were performed using a microarray. Several lncRNAs with differential expression were validated using quantitative real-time polymerase chain reaction. Gene Ontology (GO) analysis was performed to understand the functional role of the differentially expressed mRNAs. Further bioinformatics analysis was used to explore the potential function, lncRNA-mRNA correlation, and potential targets of the differentially expressed lncRNAs.
RESULTS: We found 3195 lncRNAs and 1966 mRNAs that were differentially expressed. The chromosomal distribution of the differentially expressed lncRNAs and mRNAs was unequal, with chromosome 2 having the highest number of lncRNAs and chromosome 7 having the highest number of mRNAs that were differentially expressed. Pathway analysis of the differentially expressed genes indicated the involvement of several signaling pathways including PI3K-Akt, Hippo, and pathways regulating the pluripotency of stem cells. The differentially expressed genes were also enriched for the GO terms, developmental process and muscle system process. Network analysis identified 8 statistically significant (P<.05) network objects from the upregulated lncRNAs and 3 statistically significant network objects from the downregulated lncRNAs.
CONCLUSIONS: Our results thus far imply that dysferlinopathy is associated with an aberrant expression of multiple lncRNAs, many of which may have a specific function in the disease process. GO terms and network analysis suggest a muscle-specific role for these lncRNAs. To elucidate the specific roles of these abnormally expressed noncoding RNAs, further studies engineering their expression are required.
OBJECTIVE: In this study, we compared the lncRNA and mRNA expression profiles between wild-type and dysferlin-deficient murine myoblasts (C2C12 cells).
METHODS: LncRNA and mRNA expression profiling were performed using a microarray. Several lncRNAs with differential expression were validated using quantitative real-time polymerase chain reaction. Gene Ontology (GO) analysis was performed to understand the functional role of the differentially expressed mRNAs. Further bioinformatics analysis was used to explore the potential function, lncRNA-mRNA correlation, and potential targets of the differentially expressed lncRNAs.
RESULTS: We found 3195 lncRNAs and 1966 mRNAs that were differentially expressed. The chromosomal distribution of the differentially expressed lncRNAs and mRNAs was unequal, with chromosome 2 having the highest number of lncRNAs and chromosome 7 having the highest number of mRNAs that were differentially expressed. Pathway analysis of the differentially expressed genes indicated the involvement of several signaling pathways including PI3K-Akt, Hippo, and pathways regulating the pluripotency of stem cells. The differentially expressed genes were also enriched for the GO terms, developmental process and muscle system process. Network analysis identified 8 statistically significant (P<.05) network objects from the upregulated lncRNAs and 3 statistically significant network objects from the downregulated lncRNAs.
CONCLUSIONS: Our results thus far imply that dysferlinopathy is associated with an aberrant expression of multiple lncRNAs, many of which may have a specific function in the disease process. GO terms and network analysis suggest a muscle-specific role for these lncRNAs. To elucidate the specific roles of these abnormally expressed noncoding RNAs, further studies engineering their expression are required.
摘要：
背景：长非编码RNA（lncRNA）是长度大于200个核苷酸的非编码RNA转录本，并且已知在调节涉及重要细胞功能的基因的转录中起作用。我们假设异常蛋白病中的疾病过程与lncRNAs和信使RNAs（mRNAs）的异常表达有关。
目的：在本研究中，我们比较了野生型和dhyperlin缺陷鼠成肌细胞(C2C12细胞)的lncRNA和mRNA表达谱.
方法：使用微阵列进行LncRNA和mRNA表达谱分析。使用定量实时聚合酶链反应验证了几种具有差异表达的lncRNA。进行基因本体论(GO)分析以了解差异表达的mRNA的功能作用。进一步的生物信息学分析用于探索潜在的功能，lncRNA-mRNA相关性，和差异表达lncRNAs的潜在靶标。
结果：我们发现3195个lncRNAs和1966个mRNAs差异表达。差异表达的lncRNAs和mRNAs的染色体分布不相等，染色体2具有最高数量的lncRNAs和染色体7具有最高数量的差异表达的mRNA。对差异表达基因的通路分析表明，包括PI3K-Akt，河马,和调节干细胞多能性的途径。差异表达的基因也富集了GO术语，发育过程和肌肉系统过程。网络分析鉴定了来自上调的lncRNA的8个统计学上显著(P<.05)的网络对象和来自下调的lncRNA的3个统计学上显著的网络对象。
结论：到目前为止，我们的结果暗示，异常蛋白病与多个lncRNAs的异常表达有关，其中许多可能在疾病过程中具有特定功能。GO术语和网络分析提示了这些lncRNA的肌肉特异性作用。为了阐明这些异常表达的非编码RNA的特定作用，需要进一步的研究工程他们的表达。
目的：在本研究中，我们比较了野生型和dhyperlin缺陷鼠成肌细胞(C2C12细胞)的lncRNA和mRNA表达谱.
方法：使用微阵列进行LncRNA和mRNA表达谱分析。使用定量实时聚合酶链反应验证了几种具有差异表达的lncRNA。进行基因本体论(GO)分析以了解差异表达的mRNA的功能作用。进一步的生物信息学分析用于探索潜在的功能，lncRNA-mRNA相关性，和差异表达lncRNAs的潜在靶标。
结果：我们发现3195个lncRNAs和1966个mRNAs差异表达。差异表达的lncRNAs和mRNAs的染色体分布不相等，染色体2具有最高数量的lncRNAs和染色体7具有最高数量的差异表达的mRNA。对差异表达基因的通路分析表明，包括PI3K-Akt，河马,和调节干细胞多能性的途径。差异表达的基因也富集了GO术语，发育过程和肌肉系统过程。网络分析鉴定了来自上调的lncRNA的8个统计学上显著(P<.05)的网络对象和来自下调的lncRNA的3个统计学上显著的网络对象。
结论：到目前为止，我们的结果暗示，异常蛋白病与多个lncRNAs的异常表达有关，其中许多可能在疾病过程中具有特定功能。GO术语和网络分析提示了这些lncRNA的肌肉特异性作用。为了阐明这些异常表达的非编码RNA的特定作用，需要进一步的研究工程他们的表达。
