Dataset Information

Long Noncoding RNA PART1 Promotes Hepatocellular Carcinoma Progression via Targeting miR-590-3p/HMGB2 Axis.

ABSTRACT: Introduction:In East Asia, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancer types. Long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was reported to play crucial roles in regulating cancer progression. However, roles and mechanisms of action of PART1 in hepatocellular carcinoma (HCC) still remain unknown. Methods:Quantitative real-time polymerase chain reaction (RT-qPCR) method was used to detect the PART1 expression level in HCC cells. Cell proliferation, colony formation, and transwell invasion assays were performed to investigate the biological roles of PART1 on HCC cell behaviors. Bioinformatic analysis methods were performed to analyze connections of microRNA-590-3p (miR-590-3p) with PART1 or high mobility group box 2 (HMGB2) in HCC. Moreover, expression levels of PART1, miR-590-3p, and HMGB2 in HCC tissues and normal tissues were analyzed at ENCORI. Results:PART1 expression was found to be significantly upregulated in HCC tissues and cells. Functionally, silencing of PART1 significantly suppressed HCC cell proliferation, colony formation and invasion in vitro, while forcing PART1 exerts opposite biological effects. Mechanically, miR-590-3p/HMGB2 axis was downstream target of PART1, and silencing of miR-590-3p or forcing of HMGB2 could rescue the stimulation effects of PART1 overexpression on HCC cell behaviors. Discussion:Our results provided evidence that PART1 serves as oncogenic lncRNA through sponging miR-590-3p to upregulate HMGB2 expression in HCC.

SUBMITTER: Pu J

PROVIDER: S-EPMC7502387 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long Noncoding RNA <i>PART1</i> Promotes Hepatocellular Carcinoma Progression via Targeting miR-590-3p/<i>HMGB2</i> Axis.

Pu Jian J Tan Chuan C Shao Zesheng Z Wu Xianjian X Zhang Ya Y Xu Zuoming Z Wang Jianchu J Tang Qianli Q Wei Huamei H

OncoTargets and therapy 20200916

<h4>Introduction</h4>In East Asia, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancer types. Long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (<i>PART1</i>) was reported to play crucial roles in regulating cancer progression. However, roles and mechanisms of action of <i>PART1</i> in hepatocellular carcinoma (HCC) still remain unknown.<h4>Methods</h4>Quantitative real-time polymerase chain reaction (RT-qPCR) method was used to detect the <i>PART1</i> ...[more]

PMID: 32982307

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Project description:BackgroundThough circular RNAs (circRNAs) are the key regulators in tumor carcinogenesis, they remain largely unexplored in hepatocellular carcinoma (HCC).MethodsThe expression of RanGAP1-derived circRNAs (circ_0063531, circ_0063534, circ_0063513, circ_0063518, circ_0063507, circ_0063723) were evaluated in eight paired HCC and normal tissues, and the correlation between circRanGAP1 (circ_0063531) expression and clinicopathological characteristics in 40 HCC patients was determined. The association between miR-27b-3p and circRanGAP1 or NRAS was predicted using bioinformatics analysis. The expression of circRanGAP1, miR-27b-3p, and NRAS were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The potential oncogenic role of circ-RanGAP1 was assessed using CCK-8, colony formation, transwell assays in vitro, subcutaneous tumor mouse model, vein tail metastatic model, and orthotopically implanted intrahepatic HCC model in vivo. Luciferase reporter and RNA immunoprecipitation (RIP) assays were used to explore the binding site between miR-27b-3p and circ-RanGAP1 or NRAS. Protein expression was detected using western blotting. The localization of miR-27b-3p and circ-RanGAP1 was investigated using fluorescence in situ hybridization (FISH). The level of immune infiltration was assessed by bioinformatics analysis, flow cytometry, and orthotopically implanted intrahepatic HCC models.ResultsHere, we found elevated circRanGAP1 in the cells and clinical tissues of patients with HCC. Increased circRanGAP1 levels are associated with enlarged tumors and the advanced stage of TNM. CircRanGAP1 promotes the growth, migration, and HCC cell invasion, concurrently with the growth and metastasis of tumors in-vivo. Moreover, circRanGAP1 is mainly located inside the cytoplasm. Mechanistically, circRanGAP1 as an oncogene promotes HCC progression by miR-27b-3p/NRAS/ERK axis, furthermore, affects the infiltration level of tumor-associated macrophages probably by sponging miR-27b-3p. Immune infiltration analysis shows that NRAS is positively correlated with the levels of CD68+ tumor-associated macrophages in HCC samples and that NRAS and CD68 are related to the poor outcome of HCC.ConclusionThese results reveal that circRanGAP1 is a HCC oncogene that function by the miR-27b-3p/NRAS/ERK axis and regulates the infiltration levels of tumor-associated macrophages by sponging miR-27b-3p. Therefore, circRANGAP1/ NRAS axis may be an important potential treatment target against HCC.

Dataset Information

Long Noncoding RNA PART1 Promotes Hepatocellular Carcinoma Progression via Targeting miR-590-3p/HMGB2 Axis.

Publications

Long Noncoding RNA <i>PART1</i> Promotes Hepatocellular Carcinoma Progression via Targeting miR-590-3p/<i>HMGB2</i> Axis.

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