Abstract

BackgroundBladder cancer (BC) is a common type of cancer that involves tumors of the urinary system and poses a serious threat to human health. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers. Novel lncRNA biomarkers in BC urgently need to be investigated in regard to its function and regulatory mechanisms.MethodsIdentification of differentially expressed lncRNAs in BC tissue was performed via microarray analysis. To investigate the biological functions of LINC00612, loss-of-function and gain-of-function experiments were performed in vitro and in vivo. Bioinformatics analysis, dual-luciferase reporter assays, AGO2-RIP assays, RNA pull-down assays, real-time quantitative PCR (RT-qPCR) arrays, fluorescence in situ hybridization assays, and western blot assays were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs).ResultsLINC00612 was upregulated in BC tissues and cell lines. Functionally, downregulation of LINC00612 inhibited cell proliferation and invasion in vitro and in vivo, whereas overexpression of LINC00612 resulted in the opposite effects. Bioinformatics analysis and luciferase assays revealed that miR-590 was a direct target of LINC0061, which was validated by dual-luciferase reporter assays, AGO2-RIP assays, RNA pull-down assays, RT-qPCR arrays, and rescue experiments. Additionally, miR-590 was shown to directly target the PHD finger protein 14 (PHF14) gene. LNIC00612 modulated the expression of E-cadherin and vimentin by competitively sponging miR-590 to elevate the expression of PHF14, thus affecting BC cellular epithelial-mesenchymal transition (EMT).ConclusionsOur results indicate that LINC00612 enhances the proliferation and invasion ability of BC cells by sponging miR-590 to upregulate PHF14 expression and promote BC cellular EMT, suggesting that LINC00612 may act as a potential biomarker and therapeutic target for BC.

Highlights

  • Bladder cancer is a common type of cancer involving tumors of the urinary system, has the highest published incidence involving malignant urinary system tumors, and poses a serious threat to human health

  • LINC00612 was up-regulated in Bladder cancer (BC) tissues and cell lines A total of 60 Long noncoding RNAs (lncRNAs) differentially expressed in BC tissues were screened (Fig. 1a & b)

  • The results of In situ hybridization (ISH) and RT-real-time quantitative PCR (RT-qPCR) revealed that the expression of LINC00612 was higher in tumor tissues than that in normal tissues (Fig. 1c & d)

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Summary

Introduction

Bladder cancer is a common type of cancer involving tumors of the urinary system, has the highest published incidence involving malignant urinary system tumors, and poses a serious threat to human health. The lack of specificity and sensitivity of technologies in the early diagnosis of bladder cancer, as well as the high rates of postoperative recurrence and malignant transformation following surgery, such as bladder tumor resections, are the major problems in bladder cancer diagnosis and treatment. Identification of new, highly sensitive, specific and cost-effective bladder cancer markers is needed to improve the early diagnosis rate of bladder tumors, which will have important clinical significance for improving the prognoses of patients. Bladder cancer (BC) is a common type of cancer that involves tumors of the urinary system and poses a serious threat to human health. Novel lncRNA biomarkers in BC urgently need to be investigated in regard to its function and regulatory mechanisms

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