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Microarray data re-annotation reveals specific lncRNAs and their potential functions in non-small cell lung cancer subtypes.

ABSTRACT: Non?small?cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide. The most common subtypes of NSCLC are adenocarcinoma (AC) and squamous cell carcinoma (SCC). However, the pathophysiological mechanisms contributing to AC and SCC are still largely unknown, especially the roles of long non?coding RNAs (lncRNAs). The present study identified differentially expressed lncRNAs between lung AC and SCC by re?annotation of NSCLC microarray data analysis profiling. The potential functions of lncRNAs were predicted by using coding?non?coding gene co?expressing network. Reverse transcription-quantitative polymerase chain reaction (RT?qPCR) was used to investigate lncRNA expression levels in AC cell lines (A549 and L78), SCC cell lines (H226 and H520) and normal cells (NL?20). Western blotting analysis was used to investigate the protein expression levels in these cell lines. A total of 65 lncRNAs were differentially expressed between AC and SCC including 28 lncRNAs that were downregulated in SCC subtypes compared with those in AC ones, and 37 upregulated lncRNAs in SCC subtypes compared with AC subtypes. Three lncRNAs, sex determining region Y?box 2 overlapping transcript (SOX2?OT), NCBP2 antisense RNA 2 (NCBP2?AS2) and ubiquitin like with PHD and ring finger domains 1 (UHRF1), were predicted to be associated with lung cancer; RT?qPCR confirmed that SOX2?OT and NCBP2?AS2 were associated with lung cancer. Finally, western blot assays demonstrated that there was no difference in ??catenin and glycogen synthase kinase 3? (GSK?3?) expression in cancer cells compared with NL?20, but increased phosphorylated (p?)??catenin and p?GSK?3? was detected in lung cancer cell lines compared with NL?20, particularly in A549 cells. Although these results require further experimental verification, the analysis of lncRNA signatures between AC and SCC has provided insights into the regulatory mechanism of NSCLC development.

SUBMITTER: Zhou D

PROVIDER: S-EPMC5647101 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Microarray data re-annotation reveals specific lncRNAs and their potential functions in non-small cell lung cancer subtypes.

Zhou Dongbo D Xie Mingxuan M He Baimei B Gao Ying Y Yu Qiao Q He Bixiu B Chen Qiong Q

Molecular medicine reports 20170814 4

Non‑small‑cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide. The most common subtypes of NSCLC are adenocarcinoma (AC) and squamous cell carcinoma (SCC). However, the pathophysiological mechanisms contributing to AC and SCC are still largely unknown, especially the roles of long non‑coding RNAs (lncRNAs). The present study identified differentially expressed lncRNAs between lung AC and SCC by re‑annotation of NSCLC microarray data analysis profiling. The potential functio ...[more]

PMID: 28849055

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Project description:Long non-coding RNAs (lncRNAs) have been acknowledged to serve a significant role in cancer biology and abnormal expression in tumors is frequently observed. However, their mechanisms in cervical cancer remain unclear. With a genome-wide analysis of lncRNA expression in cervical cancer tissues, the present study aimed to identify lncRNA targets for the further study of cervical cancer. To elucidate the specific role of lncRNAs in the pathogenesis of this type of cancer, 6 cervical cancer samples paired with normal cervical tissues were obtained. Expression profiles of lncRNAs and mRNAs were constructed through microarray analysis and confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) methods. Gene Ontology and pathway enrichment analyses were performed with computational methods. On the basis of correlations between the differential expression levels of lncRNAs and mRNAs, a coding-non-coding gene co-expression network (CNC network) was established. The differential expression of 5,844 lncRNAs and 4,436 mRNAs were discovered in cervical cancer samples compared with normal cervical tissues. Among the differentially expressed lncRNAs, 14 were chosen at random and validated by RT-qPCR; the majority of the results measured were consistent with the microarray results. Furthermore, the lncRNA ENST00000551152 was found to be upregulated and TCO. NS_00001368 lncRNA was downregulated in cervical cancer cell lines. The CNC network included 592 network nodes and 934 associations between 12 lncRNAs and 580 protein-coding genes, indicating that one lncRNA could act on a maximum of 141 coding genes, and that one coding gene may corresponded with a maximum of 5 lncRNAs. Overall, the present study has provided a complete expression profile of lncRNAs and mRNAs in cervical cancer, which may now be used to establish a solid foundation for cervical cancer research. These results may provide significant information for improving the understanding of the pathogenesis of cervical cancer and indicate potential therapeutic targets.

Project description:BackgroundLong non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. In this study, we aimed to investigate the lncRNA profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent, which demonstrate that the placenta is sufficient to cause this condition. Thus, we analyzed the lncRNA profiles in preeclampsia placentas.Methodology/principal findingsIn this study, we described the lncRNA profiles in six preeclampsia placentas (T) and five normal pregnancy placentas (N) using microarray. With abundant and varied probes accounting for 33,045 LncRNAs in our microarray, 28,443 lncRNAs that were expressed at a specific level were detected. From the data, we found 738 lncRNAs that were differentially expressed (? 1.5-fold-change) among preeclampsia placentas compared with controls. Coding-non-coding gene co-expression networks (CNC network) were constructed based on the correlation analysis between the differentially expressed lncRNAs and mRNAs. According to the CNC network and GO analysis of differentially expressed lncRNAs/mRNAs, we selected three lncRNAs to analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100, and CEACAMP8 were evaluated using qPCR in 40 preeclampsia placentas and 40 controls. These results revealed that three lncRNAs were aberrantly expressed in preeclampsia placentas compared with controls.Conclusions/significanceOur study is the first study to determine the genome-wide lncRNAs expression patterns in preeclampsia placenta using microarray. These results revealed that clusters of lncRNAs were aberrantly expressed in preeclampsia placenta compared with controls, which indicated that lncRNAs differentially expressed in preeclampsia placenta might play a partial or key role in preeclampsia development. Misregulation of LOC391533, LOC284100, and CEACAMP8 might contribute to the mechanism underlying preeclampsia. Taken together, this study may provide potential targets for the future treatment of preeclampsia and novel insights into preeclampsia biology.

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Microarray data re-annotation reveals specific lncRNAs and their potential functions in non-small cell lung cancer subtypes.

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Microarray data re-annotation reveals specific lncRNAs and their potential functions in non-small cell lung cancer subtypes.

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