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LncRNA GABPB1 intronic transcript 1 upregulates pigment epithelium-derived factor via miR-93 to suppress cell proliferation in hepatocellular carcinoma.

ABSTRACT: Liver cancer ranks in the top 10 most common malignancies for both mortality rate and incidence worldwide. Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer. It has been reported that long non-coding RNA GABPB1 intronic transcript 1 (IT1) is downregulated in lung cancer and predicts poor survival. However, its role in live cancer remains unclear. Therefore, the present study aimed to investigate the role of GABPB1-IT1 in HCC. A total of 64 patients with HCC (40 males and 24 females; range, 43-67 years old; mean age=55.1±5.1 years) were enrolled at the 96604 Military Hospital of the Chinese People's Liberation Army between May 2012 and May 2014. The expression levels of GABPB1-IT1 and microRNA (miR)-93 in tumor and adjacent normal tissues were measured using quantitative PCR. A dual luciferase activity assay was performed to analyze the interaction between miR-93 and GABPB1-IT1. A Cell Counting Kit-8 assay was used to analyze the effect of miR transfection on the proliferation of SNU-398 cells. It was demonstrated that GABPB1-IT1 can interact with miR-93 in HCC cells, while overexpression of GABPB1-IT1 and miR-93 in HCC cells did not affect the expression of each other. GABPB1-IT1 was downregulated in HCC tissues compared with paired non-tumor tissues and predicted poor survival. Notably, overexpression of GABPB1-IT1 in HCC cells led to upregulation of pigment epithelium-derived factor (PEDF), a target of miR-93. In addition, overexpression of GABPB1-IT1 reduced the enhancing effects of miR-93 on HCC cell proliferation. Therefore, GABPB1-IT1 may upregulate PEDF through miR-93 to suppress cell proliferation in HCC.

SUBMITTER: Li B

PROVIDER: S-EPMC7882888 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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lncRNA GABPB1 intronic transcript 1 upregulates pigment epithelium-derived factor via miR-93 to suppress cell proliferation in hepatocellular carcinoma.

Li Bin B Wei Yajun Y Ge Qinli Q Duan Yucai Y Guo Ling L

Oncology letters 20210204 4

Liver cancer ranks in the top 10 most common malignancies for both mortality rate and incidence worldwide. Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer. It has been reported that long non-coding RNA GABPB1 intronic transcript 1 (IT1) is downregulated in lung cancer and predicts poor survival. However, its role in live cancer remains unclear. Therefore, the present study aimed to investigate the role of GABPB1-IT1 in HCC. A total of 64 patients with HCC (40 males and ...[more]

PMID: 33664823

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Project description:Lipofuscin accumulates with age in the retinal pigment epithelium (RPE) in discrete granular organelles and may contribute to age-related macular degeneration. Because previous studies suggest that lipofuscin contains protein that may impact pathogenic mechanisms, we pursued proteomics analysis of lipofuscin. The composition of RPE lipofuscin and its mechanisms of pathogenesis are poorly understood in part because of the heterogeneity of isolated preparations. We purified RPE lipofuscin granules by treatment with proteinase K or SDS and showed by light, confocal, and transmission electron microscopy that the purified granules are free of extragranular material and associated membranes. Crude and purified lipofuscin preparations were quantitatively compared by (i) LC MS/MS proteomics analyses, (ii) immunoanalyses of oxidative protein modifications, (iii) amino acid analysis, (iv) HPLC of bisretinoids, and (v) assaying phototoxicity to RPE cells. From crude lipofuscin preparations 186 proteins were identified, many of which appeared to be modified. In contrast, very little protein ( approximately 2% (w/w) by amino acid analysis) and no identifiable protein were found in the purified granules, which retained full phototoxicity to cultured RPE cells. Our analyses showed that granules in purified and crude lipofuscin preparations exhibit no statistically significant differences in diameter or circularity or in the content of the bisretinoids A2E, isoA2E, and all-trans-retinal dimer-phosphatidylethanolamine. The finding that the purified granules contain minimal protein yet retain phototoxic activity suggests that RPE lipofuscin pathogenesis is largely independent of associated protein. The purified granules also exhibited oxidative protein modifications, including nitrotyrosine generated from reactive nitrogen oxide species and carboxyethylpyrrole and iso[4]levuglandin E(2) adducts generated from reactive lipid fragments. This finding is consistent with previous studies demonstrating RPE lipofuscin to be a potent generator of reactive oxygen species and supports the hypothesis that such species, including reactive fragments from lipids and retinoids, contribute to the mechanisms of RPE lipofuscin pathogenesis.

Dataset Information

LncRNA GABPB1 intronic transcript 1 upregulates pigment epithelium-derived factor via miR-93 to suppress cell proliferation in hepatocellular carcinoma.

Publications

lncRNA GABPB1 intronic transcript 1 upregulates pigment epithelium-derived factor via miR-93 to suppress cell proliferation in hepatocellular carcinoma.

Similar Datasets

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