Long noncoding RNA PCAT-1 promotes invasion and metastasis via the miR-129-5p-HMGB1 signaling pathway in hepatocellular carcinoma

• Published in: Biomedicine & pharmacotherapy Vol. 95; pp. 1187 - 1193
• Main Authors: Zhang, Deyuan, Cao, Jinyu, Zhong, Qingling, Zeng, Liangtao, Cai, Chang, Lei, Lang, Zhang, Wen, Liu, Fanrong
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.11.2017
• Subjects: Base Sequence; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Movement - genetics; Female; Gene Expression Regulation, Neoplastic; Hepatocellular carcinoma; High mobility group box 1; HMGB1 Protein - metabolism; Humans; Invasion; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-129-5p; Neoplasm Invasiveness; Neoplasm Metastasis; Prostate cancer-associated transcripts 1; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Up-Regulation - genetics; High mobility group box 1; Hepatocellular carcinoma; Invasion; Prostate cancer-associated transcripts 1; miR-129-5p
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.09.045

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. 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. 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. 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.