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Molecular Cancer Research
Molecular Cancer Research

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Chromatin, Epigenetics and RNA Regulation

Dissecting LncRNA Roles in Renal Cell Carcinoma Metastasis and Characterizing Genomic Heterogeneity by Single-Cell RNA-seq

Xue Li, Xianwen Meng, Cong Wei, Yincong Zhou, Hongjun Chen, He Huang and Ming Chen
Xue Li
Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou, China.James D. Watson Institute of Genome Sciences, Zhejiang University, Hangzhou, China.Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Xianwen Meng
Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou, China.
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Cong Wei
Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Yincong Zhou
Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou, China.
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Hongjun Chen
Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou, China.
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He Huang
Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Ming Chen
Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou, China.James D. Watson Institute of Genome Sciences, Zhejiang University, Hangzhou, China.
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  • For correspondence: mchen@zju.edu.cn
DOI: 10.1158/1541-7786.MCR-17-0776 Published December 2018
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Abstract

Long noncoding RNAs (lncRNA) have recently emerged as important regulators in cancer cell proliferation and metastasis. However, the role of lncRNAs in metastatic clear cell renal cell carcinoma (ccRCC) remains unclear. Here, single-cell RNA sequencing data were analyzed from primary renal cell carcinoma and paired metastatic renal cell carcinoma specimens, and characterized the expression profiles of over 10,000 genes, including 1,874 lncRNAs. Further analysis revealed that lncRNAs exhibit cancer type– and tissue–specific expression across ccRCC cells. Interestingly, a number of lncRNAs (n = 173) associated with ccRCC metastasis, termed ccRCC metastasis–associated lncRNAs (CMAL). Moreover, functional analysis based on a CMAL-PCG coexpression network revealed that CMALs contribute to cell adhesion, immune response, and cell proliferation. In combination with survival analysis, 12 CMALs were identified that participate in TNF and hypoxia-inducible factor 1 signaling to promote ccRCC metastasis. Further investigation on intratumoral heterogeneity showed that some CMALs are selectively expressed in different subpopulations.

Implications: To explore ccRCC metastasis, the current study performed a global dissection of lncRNAs and a complex genomic analysis of ccRCC tumor heterogeneity. The data shed light on the discovery of potential lncRNA biomarkers and lncRNA therapeutic targets.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/).

  • Received December 19, 2017.
  • Revision received March 9, 2018.
  • Accepted July 26, 2018.
  • Published first August 6, 2018.
  • ©2018 American Association for Cancer Research.
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Molecular Cancer Research: 16 (12)
December 2018
Volume 16, Issue 12
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Dissecting LncRNA Roles in Renal Cell Carcinoma Metastasis and Characterizing Genomic Heterogeneity by Single-Cell RNA-seq
Xue Li, Xianwen Meng, Cong Wei, Yincong Zhou, Hongjun Chen, He Huang and Ming Chen
Mol Cancer Res December 1 2018 (16) (12) 1879-1888; DOI: 10.1158/1541-7786.MCR-17-0776

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Dissecting LncRNA Roles in Renal Cell Carcinoma Metastasis and Characterizing Genomic Heterogeneity by Single-Cell RNA-seq
Xue Li, Xianwen Meng, Cong Wei, Yincong Zhou, Hongjun Chen, He Huang and Ming Chen
Mol Cancer Res December 1 2018 (16) (12) 1879-1888; DOI: 10.1158/1541-7786.MCR-17-0776
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