LncRNA-cCSC1 modulates cancer stem cell properties in colorectal cancer via activation of the Hedgehog signaling pathway.

Abstract

Several long noncoding RNAs (lncRNAs) have been identified in various malignant tumors and determined to contribute to the process of tumorigenesis, including that of colorectal cancer (CRC). Cancer stem cells (CSCs) have been demonstrated to promote the expansion and maintain the invasion and metastasis of cancer cells, owing to their self-renewal capacity. However, the underlying modulation mechanism of CSC-associated lncRNAs in CRC remains largely unclear. Using integrated bioinformatic analysis, we identified a novel lncRNA (lncRNA-cCSC1) that is highly expressed in CRC and colorectal cancer stem cells (CRCSCs). The biological functions of lncRNA-cCSC1 were assessed in vitro and vivo through the silencing or upregulation of its expression. The depletion of lncRNA-cCSC1 markedly inhibited the self-renewal capacity of the CRCSCs and reduced their drug resistance to 5-fluorouracil. In contrast, lncRNA-cCSC1 overexpression increased the self-renewal effect. Furthermore, aberrant lncRNA-cCSC1 expression resulted in a concomitant alteration of smoothened (SMO) and GLI family zinc finger 1 (Gli1) expression in the Hedgehog (Hh) signaling pathway. Our study is the first to identify a novel lncRNA-cCSC1 in CRC and to indicate that it may regulate CSC-like properties via the Hh signaling pathway. Thus, lncRNA-cCSC1 could be a potential biomarker and promising therapeutic target for CRC.

• Authors: He Zhou, Yongfu Xiong, Linglong Peng, Rong Wang, Hairong Zhang, Zhongxue Fu
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 121 Issue 3 Pg. 2510-2524 (03 2020) ISSN: 1097-4644 [Electronic] United States
• PMID: 31680315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Biomarkers, Tumor
• GLI1 protein, human
• Hedgehog Proteins
• RNA, Long Noncoding
• Smoothened Receptor
• Zinc Finger Protein GLI1

Topics

• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Epithelial-Mesenchymal Transition
• Female
• Gene Expression Regulation, Neoplastic
• Hedgehog Proteins (genetics, metabolism)
• Humans
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplastic Stem Cells (metabolism, pathology)
• Prognosis
• RNA, Long Noncoding (genetics)
• Smoothened Receptor (genetics, metabolism)
• Survival Rate
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• Zinc Finger Protein GLI1 (genetics, metabolism)