APC-activated long noncoding RNA inhibits colorectal carcinoma pathogenesis through reduction of exosome production
Authors: Jie-Wei Chen
Feng-Wei Wang
Yong Huang
Zhi-Cheng Xiang
Su-Fang Zhou
Chen-Hui Cao
Dan Xie
Rui-Hua Xu
Yong-Xiang Zhao
Kai Han
Xin-Yuan Guan
Mu-Yan Cai
Li-Ping Zhong
Jia-Xing Zhang
Xiao-Han Jin
Journal: Journal of Clinical Investigation (2019)
Discipline: CLINICAL MEDICINE
Keywords: Cell migration/adhesion; Colorectal cancer; Gastroenterology; Oncology.
Affiliations: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China., National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi, China., Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China., Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China.

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. 

Retracted: No

PubPeer comments:
 2021 corrigendum. https: www.jci.org articles view 149666 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. ,