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APC-activated long noncoding RNA inhibits colorectal carcinoma pathogenesis through reduction of exosome production
Feng-Wei Wang, Chen-Hui Cao, Kai Han, Yong-Xiang Zhao, Mu-Yan Cai, Zhi-Cheng Xiang, Jia-Xing Zhang, Jie-Wei Chen, Li-Ping Zhong, Yong Huang, Su-Fang Zhou, Xiao-Han Jin, Xin-Yuan Guan, Rui-Hua Xu, and Dan Xie
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Published April 1, 2021 - More info
J Clin Invest. 2021;131(7):e149666. https://doi.org/10.1172/JCI149666.
© 2021 American Society for Clinical Investigation
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Abstract
The adenomatous polyposis coli (APC) gene plays a pivotal role in the pathogenesis of colorectal carcinoma (CRC) but remains a challenge for drug development. Long noncoding RNAs (lncRNAs) are invaluable in identifying cancer pathologies and providing therapeutic options for patients with cancer. Here, we identified a lncRNA (lncRNA-APC1) activated by APC through lncRNA microarray screening and examined its expression in a large cohort of CRC tissues. A decrease in lncRNA-APC1 expression was positively associated with lymph node and/or distant metastasis, a more advanced clinical stage, as well as a poor prognosis for patients with CRC. Additionally, APC could enhance lncRNA-APC1 expression by suppressing the enrichment of PPARα on the lncRNA-APC1 promoter. Furthermore, enforced lncRNA-APC1 expression was sufficient to inhibit CRC cell growth, metastasis, and tumor angiogenesis by suppressing exosome production through the direct binding of Rab5b mRNA and a reduction of its stability. Importantly, exosomes derived from lncRNA-APC1–silenced CRC cells promoted angiogenesis by activating the MAPK pathway in endothelial cells, and, moreover, exosomal Wnt1 largely enhanced CRC cell proliferation and migration through noncanonicial Wnt signaling. Collectively, lncRNA-APC1 is a critical lncRNA regulated by APC in the pathogenesis of CRC. Our findings suggest that an APC-regulated lncRNA-APC1 program is an exploitable therapeutic approach for the treatment of patients with CRC.
Authors
Feng-Wei Wang, Chen-Hui Cao, Kai Han, Yong-Xiang Zhao, Mu-Yan Cai, Zhi-Cheng Xiang, Jia-Xing Zhang, Jie-Wei Chen, Li-Ping Zhong, Yong Huang, Su-Fang Zhou, Xiao-Han Jin, Xin-Yuan Guan, Rui-Hua Xu, Dan Xie
Original citation: J Clin Invest. 2019;129(2):727–743. https://doi.org/10.1172/JCI122478
Citation for this corrigendum: J Clin Invest. 2021;131(7):e149666. https://doi.org/10.1172/JCI149666
Following the publication of this article, the authors noted that the images presented for Figure 11D (shRNA-3 lncRNA-APC1 group) were identical to the images for Figure 7D (shRNA-3 lncRNA-APC1 exo group, capillary tube formation assay) and Supplemental Figure 8D (si-1 APC group, transwell assay), respectively. The authors have provided the correct version of Figure 11D based on the original data, and the point values in the graphs have been updated accordingly. That version is below.
The authors regret the errors.
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)