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人类胃癌中转录组范围的 piRNA 分析。

Transcriptome‑wide piRNA profiling in human gastric cancer.

机构信息

Laboratory of Radiation Oncology and Radiobiology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, P.R. China.

Department of Pathology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, P.R. China.

出版信息

Oncol Rep. 2019 May;41(5):3089-3099. doi: 10.3892/or.2019.7073. Epub 2019 Mar 18.

Abstract

Piwi‑interacting RNAs (piRNAs) comprise the largest class of non‑coding RNAs. They represent a molecular feature shared by all non‑aging biological systems, including germline and somatic cancer stem cells, which display an indefinite capacity of renewal and proliferation and are potentially immortal. They have been identified in animal stomachs, but their relationship with human gastric cancers remains largely unclear. The present study aimed to identify the piRNAs associated with human gastric cancers across the whole transcriptome. Fresh tumor tissues and adjacent non‑tumorous tissues from stomachs were examined using a piRNA microarray (23,677 piRNAs) that was then validated by qPCR. The differential expression of piRNAs between cases and controls was analyzed. The transposable elements (TEs) that are potentially targeted by the risk piRNAs were searched. The expression of the nearest genes that are complementary to the sequences of the piRNAs was examined in the stomach tissue. The regulatory effects of genome‑wide significant and replicated cancer‑risk DNA variants on the piRNA expression in stomach were tested. Based on the findings, we identified a total of 8,759 piRNAs in human stomachs. Of all, 50 were significantly (P<0.05) and differentially (>2‑fold change) expressed between the cases and controls, and 64.7% of the protein‑coding genes potentially regulated by the gastric cancer‑associated piRNAs were expressed in the human stomach. The expression of many cancer‑associated piRNAs was correlated with the genome‑wide and replicated cancer‑risk SNPs. In conclusion, we conclude that piRNAs are abundant in human stomachs and may play important roles in the etiological processes of gastric cancers.

摘要

Piwi 相互作用 RNA (piRNAs) 构成了最大的非编码 RNA 类别。它们代表了所有非衰老生物系统共有的分子特征,包括生殖系和体癌细胞干细胞,这些细胞具有无限的更新和增殖能力,并且具有潜在的永生性。它们已在动物胃中被鉴定出来,但它们与人类胃癌的关系在很大程度上仍不清楚。本研究旨在通过 piRNA 微阵列(23,677 个 piRNAs)鉴定与人类胃癌相关的 piRNAs,然后通过 qPCR 进行验证。分析了病例和对照组之间 piRNA 的差异表达。搜索潜在靶向风险 piRNA 的转座元件 (TEs)。检查与 piRNA 序列互补的胃组织中最近基因的表达。测试了全基因组显著和复制的癌症风险 DNA 变体对胃中 piRNA 表达的调节作用。根据研究结果,我们在人类胃中总共鉴定出 8759 个 piRNA。其中,有 50 个在病例和对照组之间差异表达(P<0.05),差异倍数大于 2 倍,并且 64.7%的潜在受胃癌相关 piRNA 调控的蛋白质编码基因在人类胃中表达。许多癌症相关 piRNA 的表达与全基因组和复制的癌症风险 SNPs 相关。总之,我们得出结论,piRNA 在人类胃中大量存在,可能在胃癌的发病机制中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c17/6448102/e9efb8942e8b/OR-41-05-3089-g00.jpg

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