Exosome-Derived LINC00960 and LINC02470 Promote the Epithelial-Mesenchymal Transition and Aggressiveness of Bladder Cancer Cells

Abstract

Exosomes are essential for several tumor progression-related processes, including the epithelial–mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) comprise a major group of exosomal components and regulate the neoplastic development of several cancer types; however, the progressive role of exosomal lncRNAs in bladder cancer have rarely been addressed. In this study, we identified two potential aggressiveness-promoting exosomal lncRNAs, LINC00960 and LINC02470. Exosomes derived from high-grade bladder cancer cells enhanced the viability, migration, invasion and clonogenicity of recipient low-grade bladder cancer cells and activated major EMT-upstream signaling pathways, including β-catenin signaling, Notch signaling, and Smad2/3 signaling pathways. Nevertheless, LINC00960 and LINC02470 were expressed at significantly higher levels in T24 and J82 cells and their secreted exosomes than in TSGH-8301 cells. Moreover, exosomes derived from LINC00960 knockdown or LINC02470 knockdown T24 cells significantly attenuated the ability of exosomes to promote cell aggressiveness and activate EMT-related signaling pathways in recipient TSGH-8301 cells. Our findings indicate that exosome-derived LINC00960 and LINC02470 from high-grade bladder cancer cells promote the malignant behaviors of recipient low-grade bladder cancer cells and induce EMT by upregulating β-catenin signaling, Notch signaling, and Smad2/3 signaling. Both lncRNAs may serve as potential liquid biomarkers for the prognostic surveillance of bladder cancer progression.

RETRACTED ARTICLE: Long intergenic non-protein coding RNA 960 regulates cancer cell viability, migration and invasion through modulating miR-146a-5p/interleukin 1 receptor associated kinase 1 axis in pancreatic ductal adenocarcinoma

“…Reportedly, LINC00960 expression is up-regulated in the fibroblasts of idiopathic pulmonary fibrosis, and LINC00960 negatively regulates its proliferation [25]. A recent study reports that, through up-regulating βcatenin signal, Notch signal, and Smad2/3 signal, exosome-derived LINC00960 can promote the malignant behaviors of low-grade bladder cancer cells and induce epithelial-mesenchymal transition, thus working as a potential liquid biomarker to monitor the progression of bladder cancer [26]. This study found that LINC00960 expression was up-regulated in PDAC, which is consistent with the previous report [16].…”

Biological Roles and Clinical Significance of Exosome-Derived Noncoding RNAs in Bladder Cancer

“…pointed out that exosomal lnc_00960 and lnc_02470 promoted EMT and the aggressiveness of BCa cells. They treated BCa TSGH-8301 cells with exosomes derived from BCa T24 or J82 cells, leading to decreased E-cadherin levels and increased N-cadherin, vimentin, MMP2, and MMP9 levels in TSGH-8301 cells ( 66 ). Berrondo et al.…”

Tumor heterogeneity and the potential role of liquid biopsy in bladder cancer

“…Exosomes are vesicles of endocytic origin and continuously released from the bladder [91], which can mediate communication between cells through the transfer of nucleic acids [92][93][94][95] and proteins [96] in BC. Numerous studies have been conducted to investigate the role of exosomes in patients with BC.…”