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MicroRNA-138 targets SP1 to inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells.

ABSTRACT: The identification of microRNAs (miRNAs/miRs) has enabled the improved understanding of the carcinogenesis and progression of hepatocellular carcinoma (HCC). miRNAs are small non-coding RNAs comprised of 19-24 nucleotides that regulate the expression of target genes. In the present study, miR-138 was demonstrated to be downregulated in human HCC tissues and cell lines. Restoration of miR-138 expression repressed the proliferation, migration and invasion of HCC cells. Furthermore, specificity protein 1 (SP1) was identified as a target gene of miR-138 in HCC using bioinformatics analysis, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis. Knockdown of SP1 produced similar suppressive effects to those induced by miR-138 overexpression in HCC cells. These results indicate that miR-138 targeted SP1 to repress the growth, migration and invasion of HCC cells, and may therefore represent a therapeutic target in human HCC.

SUBMITTER: Liu C

PROVIDER: S-EPMC5768080 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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MicroRNA-138 targets SP1 to inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells.

Liu Chongzhong C Zhu Jiankang J Liu Fengyue F Wang Yadong Y Zhu Min M

Oncology letters 20171108 1

The identification of microRNAs (miRNAs/miRs) has enabled the improved understanding of the carcinogenesis and progression of hepatocellular carcinoma (HCC). miRNAs are small non-coding RNAs comprised of 19-24 nucleotides that regulate the expression of target genes. In the present study, miR-138 was demonstrated to be downregulated in human HCC tissues and cell lines. Restoration of miR-138 expression repressed the proliferation, migration and invasion of HCC cells. Furthermore, specificity pro ...[more]

PMID: 29387246

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Project description:Many studies have recently suggested that microRNAs (miRNAs) contribute to the development of various types of human cancers as well as to their invasive and metastatic capacities. Previously, our miRNA expression signature of renal cell carcinoma (RCC) revealed that microRNA?138 (miR?138) was significantly reduced in cancer cells. The aim of the present study was to investigate the functional significance of miR?138 and to identify its target genes in RCC cells. Restoration of mature miR?138 in two RCC cell lines (A498 and 786?O) caused changes in the bleb-like cell morphology, characteristics of the epithelial-mesenchymal transition (EMT). Restoration also significantly inhibited migration and invasion in the two RCC cell lines, suggesting that miR?138 functions as a tumor suppressor. Genome-wide gene expression analysis (miR?138 transfectants and RCC clinical specimens) and TargetScan database studies showed that vimentin (VIM) is a promising candidate target gene of miR?138. It is well known that VIM is one of the most widely expressed mammalian intermediate filament proteins. Recent studies showed that VIM functions in cell adhesion, migration, survival and cell signaling processes via dynamic assembly/disassembly in cancer cells. We focused on VIM and investigated whether VIM was regulated by tumor suppressive miR?138 and contributed to cancer cell migration and invasion in RCC cells. Restoration of miR?138 in RCC cell lines suppressed VIM expression at both the mRNA and protein levels. Silencing studies of VIM in RCC cell lines demonstrated significant inhibition of cell migration and invasion activities in si-VIM transfectants. In clinical specimens of RCC, the expression levels of VIM were significantly upregulated in cancer tissues compared to adjacent non-cancerous tissues. Furthermore, immunohistochemistry showed that VIM expression levels in RCC specimens were significantly higher than those in normal renal tissues. These data suggest that VIM may function as an oncogene and is regulated by tumor suppressive miR?138. The existence of a tumor suppressive miR?138-mediated oncogenic pathway provides new insights into the potential mechanisms of RCC oncogenesis and metastasis.

Dataset Information

MicroRNA-138 targets SP1 to inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells.

Publications

MicroRNA-138 targets SP1 to inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells.

Similar Datasets

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