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Circulating lncRNA UCA1 Promotes Malignancy of Colorectal Cancer via the miR-143/MYO6 Axis

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机构: [1]Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming 650224, China [2]Department of Gastrointestinal, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Nanjing 650021, China [3]Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [4]Department of Physical Education, Yunnan Normal University, Kunming 650500, China [5]Department of Bioengineering, College of Life Science, Lomonosov Moscow State University, Moscow 119991, Russia [6]Department of Life Technology Teaching and Research, College of Life Sciences, Southwest Forestry University, Kunming 650224, China [7]Department of Gastrointestinal Surgery, Sixth People’s Hospital of Dalian City, Dalian 116031, China [8]Key Laboratory of Forest Biotechnology in Yunnan, Southwest Forestry University, No. 300 Bailong Temple, Panlong, Kunming, Yunnan 652400, China.
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Exosomes mediate cell-cell crosstalk in cancer progression by transferring a variety of biomolecules, including long noncoding RNAs (lncRNAs). Long non-coding RNA urothelial carcinoma-associated (UCA1) is a well-known lncRNA associated with the development and progression of various cancers, including colorectal cancer (CRC). However, the presence of UCA1 in exosomes and the roles and clinical values of exosomal UCA1 in CRC remain unknown. In this study, we systematically analyzed the expression profiles of exosomal lncRNAs in CRC patients using a high-throughput microarray assay. Then, we evaluated the UCA1 expression levels in a series of CRC tissues and the serum exosomes of CRC patients using quantitative real-time PCR. The roles of UCA1 on CRC in vitro and in vivo were investigated by MTT, colony formation, Transwell, quantitative real-time PCR, flow cytometry, and western blotting. The miRNA binding sites of UCA1 were predicted using the miRcode online database, and miR-143 was validated to target UCA1 by dual-luciferase activity assay and AGO2 RNA immunoprecipitation. Finally, the role of exosome-mediated UCA1 was further investigated by co-culturing with CRC cells. This study showed that UCA1 was upregulated in CRC tissues and functioned as an oncogene in CRC. Loss-of-function investigations showed that inhibition of UCA1 suppressed CRC cell proliferation and metastasis in vivo and in vitro. Mechanistically, UCA1 was identified as a miR-143 sponge. We also found that MYO6 was a direct target of miR-1205, which functioned as an oncogene in CRC. Moreover, UCA was also upregulated in the serum exosomes of CRC patients and could transfer UCA1 to CRC cells to increase their abilities of cell proliferation and migration. In conclusion, these data suggest that UCA1 could be an oncogene for CRC and may serve as a candidate target for new therapies in human CRC.Copyright © 2019. Published by Elsevier Inc.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验
第一作者:
第一作者机构: [1]Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming 650224, China [8]Key Laboratory of Forest Biotechnology in Yunnan, Southwest Forestry University, No. 300 Bailong Temple, Panlong, Kunming, Yunnan 652400, China. [*1]Key Laboratory of Forest Biotechnology in Yunnan, Southwest Forestry University, No. 300 Bailong Temple, Panlong, Kunming, Yunnan 652400, China.
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通讯作者:
通讯机构: [1]Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming 650224, China [8]Key Laboratory of Forest Biotechnology in Yunnan, Southwest Forestry University, No. 300 Bailong Temple, Panlong, Kunming, Yunnan 652400, China. [*1]Key Laboratory of Forest Biotechnology in Yunnan, Southwest Forestry University, No. 300 Bailong Temple, Panlong, Kunming, Yunnan 652400, China.
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