RAB27B-activated secretion of stem-like tumor exosomes delivers the biomarker microRNA-146a-5p, which promotes tumorigenesis and associates with an immunosuppressive tumor microenvironment in colorectal cancer

Wei Chung Cheng, Tsai Tsen Liao, Chun Chi Lin, Lan Ting Emily Yuan, Hsin Yi Lan, Hung Hsin Lin, Hao Wei Teng, Hsin Chuan Chang, Chi Hung Lin, Chih Yung Yang, Shih Ching Huang, Jeng Kai Jiang, Shung Haur Yang, Muh Hwa Yang, Wei Lun Hwang

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The dynamic cell–cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are extracellular vesicles that actively participate in cell–cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the β-catenin/Tcf-4-activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA-146a-5p (miR-146a) is the major miRNA in CRCSC exosomes and exosomal miR-146a promotes stem-like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR-146a expression in serum exhibits higher miR-146a High /Numb Low CRCSC traits, an increased number of tumor-filtrating CD66(+) neutrophils and a decreased number of tumor-infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome-mediated stemness expansion.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Exosomes
Tumor Microenvironment
Immunosuppressive Agents
MicroRNAs
Neoplastic Stem Cells
Colorectal Neoplasms
Carcinogenesis
Biomarkers
Neoplasms
RNA Sequence Analysis
Catenins
Retroelements
Neutrophils
Homeostasis
Communication
RNA
T-Lymphocytes
Serum

Keywords

  • cancer stem cells
  • exosome heterogeneity
  • microRNA biomarker

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

RAB27B-activated secretion of stem-like tumor exosomes delivers the biomarker microRNA-146a-5p, which promotes tumorigenesis and associates with an immunosuppressive tumor microenvironment in colorectal cancer. / Cheng, Wei Chung; Liao, Tsai Tsen; Lin, Chun Chi; Yuan, Lan Ting Emily; Lan, Hsin Yi; Lin, Hung Hsin; Teng, Hao Wei; Chang, Hsin Chuan; Lin, Chi Hung; Yang, Chih Yung; Huang, Shih Ching; Jiang, Jeng Kai; Yang, Shung Haur; Yang, Muh Hwa; Hwang, Wei Lun.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Cheng, Wei Chung ; Liao, Tsai Tsen ; Lin, Chun Chi ; Yuan, Lan Ting Emily ; Lan, Hsin Yi ; Lin, Hung Hsin ; Teng, Hao Wei ; Chang, Hsin Chuan ; Lin, Chi Hung ; Yang, Chih Yung ; Huang, Shih Ching ; Jiang, Jeng Kai ; Yang, Shung Haur ; Yang, Muh Hwa ; Hwang, Wei Lun. / RAB27B-activated secretion of stem-like tumor exosomes delivers the biomarker microRNA-146a-5p, which promotes tumorigenesis and associates with an immunosuppressive tumor microenvironment in colorectal cancer. In: International Journal of Cancer. 2019.
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abstract = "The dynamic cell–cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are extracellular vesicles that actively participate in cell–cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the β-catenin/Tcf-4-activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA-146a-5p (miR-146a) is the major miRNA in CRCSC exosomes and exosomal miR-146a promotes stem-like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR-146a expression in serum exhibits higher miR-146a High /Numb Low CRCSC traits, an increased number of tumor-filtrating CD66(+) neutrophils and a decreased number of tumor-infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome-mediated stemness expansion.",
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AU - Lin, Chun Chi

AU - Yuan, Lan Ting Emily

AU - Lan, Hsin Yi

AU - Lin, Hung Hsin

AU - Teng, Hao Wei

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AU - Lin, Chi Hung

AU - Yang, Chih Yung

AU - Huang, Shih Ching

AU - Jiang, Jeng Kai

AU - Yang, Shung Haur

AU - Yang, Muh Hwa

AU - Hwang, Wei Lun

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