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环状 RNA 相关 ceRNA 网络揭示了下咽癌中的 ErbB 和 Hippo 信号通路。

CircRNA-associated ceRNA network reveals ErbB and Hippo signaling pathways in hypopharyngeal cancer.

机构信息

The Second Department of Otolaryngology, Head and Neck Surgery of The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650223, P.R. China.

Department of Otolaryngology Head and Neck Surgery, Chinese PLA Kunming General Hospital, Kunming, Yunnan 650118, P.R. China.

出版信息

Int J Mol Med. 2019 Jan;43(1):127-142. doi: 10.3892/ijmm.2018.3942. Epub 2018 Oct 19.

DOI:10.3892/ijmm.2018.3942
PMID:30365065
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6257835/
Abstract

Accumulating evidence has suggested that circular RNAs (circRNAs), a novel class of non‑coding RNAs, have crucial roles in tumor progression. However, the significance of circRNAs in hypopharyngeal cancer (HCa) remains to be investigated. The present study has identified aberrantly expressed circRNAs by performing circRNA sequencing analyses of three pairs of tumor and adjacent normal samples from patients with HCa. The results demonstrated that 173 circRNAs were differentially expressed (DE), including 71 upregulated and 102 downregulated circRNAs (FDR<0.05 and fold changes of ≥2 or ≤0.5 by Mann‑Whitney U test followed by Benjamini‑Hochberg correction for multiple testing). Pathway analyses of the genes producing DE circRNAs revealed that many of them were involved in cancer‑related pathways. To further illustrate the roles of circRNAs in HCa progression, a competing endogenous RNA (ceRNAs) network was constructed, consisting of circRNAs, miRNA, and miRNA targeted genes. The results demonstrated that multiple cancer‑related pathways were affected by performing enrichment analyses of the targeted genes. Of note, a ceRNA subnetwork was isolated, consisting of two circRNAs (hsa_circ_0008287 and hsa_circ_0005027) and one miRNA (hsa‑miR‑548c‑3p), which significantly affect both ErbB and Hippo signaling pathways. In conclusion, the present study identified a set of circRNAs that are potentially implicated in the tumorigenesis of HCa and may serve as potential biomarkers for the diagnosis of HCa.

摘要

越来越多的证据表明,环状 RNA(circRNA)作为一类新型的非编码 RNA,在肿瘤进展中发挥着关键作用。然而,circRNA 在下咽癌(HCa)中的意义仍有待研究。本研究通过对 3 对 HCa 患者肿瘤组织和相邻正常组织的 circRNA 测序分析,鉴定出了异常表达的 circRNA。结果表明,有 173 个 circRNA 存在差异表达(DE),包括 71 个上调和 102 个下调的 circRNA(FDR<0.05,Mann-Whitney U 检验的倍数变化≥2 或≤0.5,并用 Benjamini-Hochberg 多重检验校正)。对 DE circRNA 产生的基因进行通路分析表明,其中许多基因参与了癌症相关通路。为了进一步说明 circRNA 在 HCa 进展中的作用,构建了一个竞争性内源 RNA(ceRNA)网络,包括 circRNA、miRNA 和 miRNA 靶向基因。结果表明,通过对靶向基因进行富集分析,多个癌症相关通路受到影响。值得注意的是,分离出了一个包含两个 circRNA(hsa_circ_0008287 和 hsa_circ_0005027)和一个 miRNA(hsa-miR-548c-3p)的 ceRNA 子网络,该子网络显著影响 ErbB 和 Hippo 信号通路。总之,本研究鉴定了一组可能参与 HCa 发生的 circRNA,它们可能作为 HCa 诊断的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/2f60183c3d3c/IJMM-43-01-0127-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/5e89e4fd1b06/IJMM-43-01-0127-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/59604b3f0d1b/IJMM-43-01-0127-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/7d426de3997b/IJMM-43-01-0127-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/f12886b6c345/IJMM-43-01-0127-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/de4415fa432e/IJMM-43-01-0127-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/2f60183c3d3c/IJMM-43-01-0127-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/5e89e4fd1b06/IJMM-43-01-0127-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/3d513fcb9717/IJMM-43-01-0127-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/b86e95c56070/IJMM-43-01-0127-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/59604b3f0d1b/IJMM-43-01-0127-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/7d426de3997b/IJMM-43-01-0127-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/f12886b6c345/IJMM-43-01-0127-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/de4415fa432e/IJMM-43-01-0127-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0352/6257835/2f60183c3d3c/IJMM-43-01-0127-g07.jpg

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