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Decreased expression of LncRNA SLC25A25-AS1 promotes proliferation, chemoresistance, and EMT in colorectal cancer cells

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Tumor Biology

Abstract

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are aberrantly expressed in colorectal cancer (CRC); however, only few CRC-related lncRNAs have been characterized. In this study, we aimed to dig out potential dysregulated lncRNAs that are highly involved in CRC development. Using a lncRNA-mining approach, we performed lncRNA expression profiling in a large CRC cohort from Gene Expression Ominus (GEO), GSE39582 test series (N = 585). We identified 31 downregulated lncRNAs and 16 upregulated lncRNAs from the GSE39582 test series patients (566 tumor patients and 19 normal controls). The reliability of lncRNA expression profiles was further confirmed by RT-qPCR in carcinoma tissues and paired adjacent normal tissues from 30 CRC patients, also in the serum from 109 CRC patients, and 99 normal individuals. We demonstrated that the expression of SLC25A25-AS1, which has not been reported previously, was significantly decreased in both the tumor tissues (27 out of 30) and serum of CRC patients. SLC25A25-AS1 overexpression significantly inhibited proliferation and colony formation in colorectal cancer cell lines, and downregulation of SLC25A25-AS1 obviously enhanced chemoresistance and promoted EMT process in vitro associated with Erk and p38 signaling pathway activation. Therefore, SLC25A25-AS1 was determined to play a tumor suppressive role in CRC. Our results might provide a lncRNA-based target for CRC treatment.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81472208).

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Authors and Affiliations

  1. Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China

    Yuan Li, Shengkai Huang, Yan Li, Weilong Zhang, Mei Zhao, Hong Lin, Dongdong Li & Changzhi Huang

  2. Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, 100730, China

    Kun He

  3. Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Honggang Zhang

  4. Department of Abdomen Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Zhaoxu Zheng

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  1. Yuan Li
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Fig. S1

The characterization of SLC25A25-AS1 (a). The nucleotide sequence of full-length human SLC25A25-AS1. b Putative proteins possibly encoded by SLC25A25-AS1 as predicted by the ORF Finder. c UCSC txCdsPredict score of SLC25A25-AS1 is 192.0 (GIF 389 kb)

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Li, Y., Huang, S., Li, Y. et al. Decreased expression of LncRNA SLC25A25-AS1 promotes proliferation, chemoresistance, and EMT in colorectal cancer cells. Tumor Biol. 37, 14205–14215 (2016). https://doi.org/10.1007/s13277-016-5254-0

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