LncRNA LINC00355 promotes EMT and metastasis of bladder cancer cells through the miR-424-5p/HMGA2 axis

Abstract

Bladder cancer is a common malignant tumor with a high recurrence rate and mortality, while the detailed mechanisms for bladder cancer progression and metastasis are unknown. Recently, long non-coding RNAs (lncRNAs) are reported to be involved in the development of cancers. In this study, we aim to investigate the role of lncRNA LINC00355 in bladder cancer progression and metastasis. The association between LINC00355 and the prognosis of bladder cancer patients was determined by Kaplan-Meier survival analysis. Cell migration and invasion ability were detected using the Transwell migration and invasion assay. The relationships of LINC00355, miR-424-5p, and High Mobility Group AT-Hook 2 (HMGA2) were verified through the luciferase assay and RNA pull-down assay. Xenograft tumor was established to evaluated tumor lung metastasis in vivo.qRT-PCR and western blot were used to detect gene expression. LINC00355 was upregulated in bladder cancer patients, especially in patients with higher TNM stage. Elevated LINC00355 was correlated with the poor prognosis of bladder cancer patients. Besides, overexpressed LINC00355 promoted migration, invasion, and epithelial-mesenchymal transition (EMT) ability of bladder cancer cells. Contrarily, decreased LINC00355 suppressed migration, invasion, and EMT ability of bladder cancer cells and lung metastasis of xenograft tumors. Furthermore, LINC00355 could regulate HMGA2 expression by acting as a sponge for miR-424-5p. Overexpression of HMGA2 induced EMT of bladder cancer cells. Additionally, LINC00355 regulated the migration, invasion, and EMT ability of bladder cancer cells through modulating HMGA2 expression via sponging miR-424-5p. LINC00355 promoted migration, invasion, and EMT ability of bladder cancer through elevating HMGA2 expression via acting as a sponge for miR-424-5p.

E2F1 promotes cell migration in hepatocellular carcinoma via FNDC3B

“…In this study, we did not identify any transcriptional inhibitors to support our hypothesis regarding feedback inhibition. However, several non‐coding RNAs have been found to regulate FNDC3B expression in other cancers recently [ 14 , 36 , 37 ]. We will further investigate the potential role of these non‐coding RNAs in feedback inhibition of FNDC3B expression.…”

Current insights into the oncogenic roles of lncRNA LINC00355

“…LINC00355 promoted tumor metastasis in vivo in a xenograft mouse model through the LINC00355/miR-424-5p/HMGA2 axis in BCa [13].…”

The Roles of miRNAs in Predicting Bladder Cancer Recurrence and Resistance to Treatment

“…There is a significant body of work investigating the role of EMT in BCa, especially with respect to recurrence and chemoresistance, the central themes of this review. Specifically, studies have looked at EMT-related genes to predict prognostic outcomes in patients with BCa [ 50 , 69 ] and at the role of non-coding RNAs that regulate the EMT pathway through axes involving miRNAs [ 70 , 71 ]. One important group of miRNAs involved in BCa EMT is the miR-200 family: work has shown that miR-200c and miR-200b inhibit EMT [ 72 , 73 ], and miR-200 expression is broadly linked to improved bladder cancer survival [ 74 ].…”