单细胞和结直肠癌转录组整合分析鉴定的细胞类型特异性长非编码 RNA 靶标。

Cell type specific long non-coding RNA targets identified by integrative analysis of single-cell and bulk colorectal cancer transcriptomes.

机构信息

Department for BioMedical Research, University of Bern, 3008, Bern, Switzerland.

Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland.

出版信息

Sci Rep. 2024 May 13;14(1):10939. doi: 10.1038/s41598-024-61430-7.

DOI:10.1038/s41598-024-61430-7

PMID:38740871

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11091208/

Abstract

Long non-coding RNAs (lncRNAs) represent an emerging class of genes which play significant and diverse roles in human cancers. Nevertheless, the functional repertoires of lncRNAs in cancer cell subtypes remains unknown since most studies are focused on protein coding genes. Here, we explored the contribution of lncRNAs in Colorectal Cancer (CRC) heterogeneity. We analyzed 49'436 single-cells from 29 CRC patients and showed that lncRNAs are significantly more cell type specific compared to protein-coding genes. We identified 996 lncRNAs strongly enriched in epithelial cells. Among these, 98 were found to be differentially expressed in tumor samples compared to normal controls, when integrating 270 bulk CRC profiles. We validated the upregulation of two of them (CASC19 and LINC00460) in CRC cell lines and showed their involvement in CRC proliferation by CRISPR-Cas9 knock down experiments. This study highlights a list of novel RNA targets for potential CRC therapeutics, substantiated through experimental validation.

摘要

长链非编码 RNA（lncRNA）是一类新兴的基因，在人类癌症中发挥着重要且多样的作用。然而，由于大多数研究都集中在蛋白质编码基因上，lncRNA 在癌症细胞亚型中的功能谱仍然未知。在这里，我们探讨了 lncRNA 在结直肠癌（CRC）异质性中的贡献。我们分析了 29 名 CRC 患者的 49436 个单细胞，结果表明，lncRNA 比蛋白质编码基因更具有细胞类型特异性。我们鉴定了 996 个在上皮细胞中强烈富集的 lncRNA。其中，有 98 个在与正常对照相比的肿瘤样本中差异表达，当整合 270 个 CRC 批量图谱时。我们验证了其中两个（CASC19 和 LINC00460）在 CRC 细胞系中的上调，并通过 CRISPR-Cas9 敲低实验表明它们参与了 CRC 的增殖。这项研究通过实验验证，突出了一系列用于潜在 CRC 治疗的新型 RNA 靶标。