LncRNA-cCSC1 modulates cancer stem cell properties in colorectal cancer via activation of the Hedgehog signaling pathway |
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Authors: | He Zhou Yongfu Xiong Linglong Peng Rong Wang Hairong Zhang Zhongxue Fu |
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Affiliation: | 1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;2. The First Department of Hepatobiliary Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China;3. Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China;4. Department of Gastrointestinal Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China |
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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. |
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Keywords: | cancer stem cells colorectal cancer Hedgehog long noncoding RNA stemness |
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