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Long non-coding RNA LUCAT1 promotes tumourigenesis by inhibiting ANXA2 phosphorylation in hepatocellular carcinoma.

ABSTRACT: Long non-coding RNAs (lncRNAs) play essential roles in diverse biological processes; however, current understanding of the mechanism underlying the regulation of tumour proliferation and metastasis is limited. Lung cancer-associated transcript 1 (LUCAT1) has been reported in a variety of human cancers, while its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to determine the biological role and underlying mechanism of LUCAT1 on progression and metastasis in HCC cells and clinical specimens. Our results demonstrated that LUCAT1 was up-regulated in HCC tissues and cells. Loss- and gain-of-function studies revealed that LUCAT1 promotes the proliferation and metastasis of HCC cells in vitro and in vivo. Furthermore, RNA pulldown and Western blot assays indicated that LUCAT1 inhibited the phosphorylation of Annexin A2 (ANXA2) to reduce the degradation of ANXA2-S100A10 heterotetramer (AIIt), which in turn accelerated the secretion of plasminogen into plasmin, thereby resulting in the activation of metalloprotease proteins. In conclusion, we propose that LUCAT1 serves as a novel diagnostic and therapeutic target for HCC.

SUBMITTER: Lou Y

PROVIDER: S-EPMC6378214 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Long non-coding RNA LUCAT1 promotes tumourigenesis by inhibiting ANXA2 phosphorylation in hepatocellular carcinoma.

Lou Yun Y Yu Yue Y Xu Xiaolia X Zhou Shu S Shen Haiyuan H Fan Tianlong T Wu Di D Yin Jie J Li Guoqiang G

Journal of cellular and molecular medicine 20181226 3

Long non-coding RNAs (lncRNAs) play essential roles in diverse biological processes; however, current understanding of the mechanism underlying the regulation of tumour proliferation and metastasis is limited. Lung cancer-associated transcript 1 (LUCAT1) has been reported in a variety of human cancers, while its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to determine the biological role and underlying mechanism of LUCAT1 on progression and metastasis in HCC cells an ...[more]

PMID: 30588744

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Project description:BackgroundHepatocellular carcinoma (HCC) is still the most common cause of tumor-related death worldwide and accumulating studies report that long non-coding RNAs (LncRNAs) are closely related with HCC development, metastasis and prognosis. Cisplatinum, a well-known chemotherapeutic drug, has been widely used for treatment of numerous human cancers including HCC. This study aimed to investigate the differential expressions of LncRNAs in HCC cells treated with cisplatinum and its underlying mechanism.MethodsThe differential expressions of LncRNAs in HCC cells treated with cisplatinum were determined by RNA-seq. The roles of TPTEP1 in HCC development by applying gene function gain and loss analysis in MHCC97H and QYG-7703 cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR), cell proliferation, colony formation, cell invasion and flow cytometry assays. The underlying mechanism of TPTEP1 sensitizing hepatocellular carcinoma cells to cisplatinum was examined by RNA-pull down, western blotting, subcellular fractionation, RNA immunoprecipitation and dual luciferase reporter assays. The effect of TPTEP1 on tumorigenesis in vivo was performed with a subcutaneous xenograft mouse model of HCC. In addition, TPTEP1 expression was detected in clinical tumor tissue samples by qRT-PCR.ResultsLncRNA TPTEP1 was highly expressed in cisplatinum-treated HCC cells, which sensitizes hepatocellular carcinoma cell to cisplatinum-induced apoptosis. TPTEP1 overexpression inhibited, while TPTEP1 knockdown promoted HCC cell proliferation, tumorigenicity and invasion. Furthermore, TPTEP1 exerted its tumor suppressing activities by interacting with signal transducer and activator of transcription 3 (STAT3) to inhibit its phosphorylation, homodimerization, nuclear translocation and down-stream genes transcription. Moreover, TPTEP1 overexpression obviously inhibits tumor masses in vivo in a subcutaneous xenograft mouse model of HCC and TPTEP1 is frequently downregulated in HCC tissues, compared to its corresponding pre-tumor tissues.ConclusionLncRNA TPTEP1 inhibits hepatocellular carcinoma cells progression by affecting IL-6/STAT3 signaling. Taken together, our findings suggest a tumor suppressing role of TPTEP1 in HCC progression and provide a novel understanding of TPTEP1 during the chemotherapy for HCC.

Dataset Information

Long non-coding RNA LUCAT1 promotes tumourigenesis by inhibiting ANXA2 phosphorylation in hepatocellular carcinoma.

Publications

Long non-coding RNA LUCAT1 promotes tumourigenesis by inhibiting ANXA2 phosphorylation in hepatocellular carcinoma.

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