Functional analysis of miR-375 in oral squamous cell carcinoma cells
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ABSTRACT:
PROVIDER: PRJNA1003484 | ENA |
REPOSITORIES: ENA
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Project description:Recently, a number of tumor suppressive microRNAs (TS-miRs) have been found in human ma-lignancies. In this study, we have attempted to identify a novel TS-miR in oral squamous cell carcinoma (OSCC) using function-based screening. First, we transfected human OSCC cells with 968 synthetic mimicking human mature miRs individually, and then the growth of these cells was evaluated. Five miRs significantly reduced the cell growth rate by less than 30%, and miR-1289 had the most potent growth inhibitory effect among these miRs. Next, miR-1289/atelocollagen complex administration significantly reduced the size of subcutaneously xenografted human OSCC tumors. Furthermore, the expression levels of miR-1289 were significant decreased in OSCC tissues compared to adjacent normal oral mucosa. Finally, we identified magnesium transporter 1 as a target gene of miR-1289. These results suggest that miR-1289 functions as a novel TS-miR in OSCC, and may be a useful therapeutic tool for the patients with OSCC. We explored the target genes of miR-1289 in human oral squamous cell carcinoma cells using microarray analysis.
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Project description:Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor associated with poor prognosis. MicroRNAs (miRNAs) play crucial regulatory roles in the cancer development. However, the role of miRNAs in OSCC development and progression is not well understood. Methods: We sought to establish a dynamic Chinese hamster OSCC animal model, construct miRNA differential expression profiles of its occurrence and development, predict its targets, and perform functional analysis and validation in vitro. Results: Using expression and functional analyses, the key candidate miRNA (miR-181a-5p) was selected for further functional research, and the expression of miR-181a-5p in OSCC tissues and cell lines was detected. Subsequently, transfection technology and a nude mouse tumorigenic model were used to explore potential molecular mechanisms. miR-181a-5p was significantly downregulated in human OSCC specimens and cell lines, and decreased miR-181a-5p expression was observed in multiple stages of the Chinese hamster OSCC animal model. Moreover, upregulated miR-181a-5p significantly inhibited OSCC cell proliferation, colony formation, invasion, and migration; blocked the cell cycle; and promoted apoptosis. BCL2 was identified as a target of miR-181a-5p. BCL2 may interact with apoptosis- (BAX), invasion- and migration- (TIMP1, MMP2, and MMP9), and cell cycle-related genes (KI67, E2F1, CYCLIND1, and CDK6) to further regulate biological behavior. Tumor xenograft analysis indicated that tumor growth was significantly inhibited in the high miR-181a-5p expression group. Conclusions: Our findings indicate that miR-181a-5p can be used as a potential biomarker and provide a novel animal model for mechanistic research on oral cancer.
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