Deyuan Zhang1, Jinyu Cao2, Qingling Zhong3, Liangtao Zeng1, Chang Cai1, Lang Lei1, Wen Zhang1, Fanrong Liu4. 1. Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. 2. Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, China; Molecular Biology Center, The Second Affiliated Hospital of Nanchang University, Nanchang, China. 3. Department of Basic Nursing, Medical College of Nanchang University, Nanchang, China. 4. Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. Electronic address: liufanrong@163.com.
Abstract
OBJECTIVE: The long non-coding RNA (lncRNA) prostate cancer-associated transcript 1(PCAT-1) has been shown to be dysregulated and exert vital roles in tumorigenesis and progression of various malignancies. However, the precise molecular mechanism in the metastasis and invasion of HCC remain unclear. METHODS: The expression levels of PCAT1 derived from human HCC tissues and cell lines were analyzed through quantitative real-time PCR. QRT-PCR was also applied to detect the expression of HMGB1 and miR-129-5p. Wound healing assay and transwell assays were performed to analyze cell migration and invasion ability. The mRNA levels and protein expression of HMGB1 were detected by western-blotting analysis and immunohistochemistry, respectively. Luciferase assays were used to investigate binding seeds beteen miRNA-129-5p and other transcripts, such as PCAT-1, HMGB1. RESULT: In this study, our founding demonstrated that PCAT-1 was not only aberrantly upregulated in HCC tissues and cell lines, but also associated with TNM stage, metastasis and Histological grade. In vitro, downregulation of PCAT-1 could reduce the invasion and migration of HCC cells. Moreover, our results showed that PCAT-1 could act as an endogenous RNA by directly binding to miR-129-5p. In addition, Luciferase reporter assay and western blotting analyses showed that PCAT-1 repressed inhibitory effect of miR-129-5p and reverse high mobility group box 1 (HMGB1) expression, a target gene of miR-129-5p. CONCLUSION: PCAT-1 functions as competing endogenous RNA (ceRNA) to provide a better understanding for HCC metastasis, and serves as a potential diagnostic and therapeutic target via PCAT-1/miR-129-5p/HMGB1 regulatory crosstalk for the deadly disease.
OBJECTIVE: The long non-coding RNA (lncRNA) prostate cancer-associated transcript 1(PCAT-1) has been shown to be dysregulated and exert vital roles in tumorigenesis and progression of various malignancies. However, the precise molecular mechanism in the metastasis and invasion of HCC remain unclear. METHODS: The expression levels of PCAT1 derived from human HCC tissues and cell lines were analyzed through quantitative real-time PCR. QRT-PCR was also applied to detect the expression of HMGB1 and miR-129-5p. Wound healing assay and transwell assays were performed to analyze cell migration and invasion ability. The mRNA levels and protein expression of HMGB1 were detected by western-blotting analysis and immunohistochemistry, respectively. Luciferase assays were used to investigate binding seeds beteen miRNA-129-5p and other transcripts, such as PCAT-1, HMGB1. RESULT: In this study, our founding demonstrated that PCAT-1 was not only aberrantly upregulated in HCC tissues and cell lines, but also associated with TNM stage, metastasis and Histological grade. In vitro, downregulation of PCAT-1 could reduce the invasion and migration of HCC cells. Moreover, our results showed that PCAT-1 could act as an endogenous RNA by directly binding to miR-129-5p. In addition, Luciferase reporter assay and western blotting analyses showed that PCAT-1 repressed inhibitory effect of miR-129-5p and reverse high mobility group box 1 (HMGB1) expression, a target gene of miR-129-5p. CONCLUSION:PCAT-1 functions as competing endogenous RNA (ceRNA) to provide a better understanding for HCC metastasis, and serves as a potential diagnostic and therapeutic target via PCAT-1/miR-129-5p/HMGB1 regulatory crosstalk for the deadly disease.
Authors: Cristian Arriaga-Canon; Inti Alberto De La Rosa-Velázquez; Rodrigo González-Barrios; Rogelio Montiel-Manríquez; Diego Oliva-Rico; Francisco Jiménez-Trejo; Carlo Cortés-González; Luis A Herrera Journal: Oncotarget Date: 2018-04-17