4.6 Article

TCF21 regulates miR-10a-5p/LIN28B signaling to block the proliferation and invasion of melanoma cells

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PLOS ONE
卷 16, 期 8, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0255971

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The study confirmed that miR-10a-5p had lower expression in melanoma cells and high expression suppressed the proliferation, migration, and invasion abilities. It was also found that miR-10a-5p targeted LIN28B mRNA and decreased LIN28B protein expression. TCF21 upregulation led to decreased LIN28B expression and increased miR-10a-5p expression, revealing a potential regulatory relationship between TCF21 and miR-10a-5p in melanoma.
Background and aim Some research has suggested that miRNA-10a (miR-10a-5p) had an inhibitory function in proliferation and invasion of cancers. Whereas the role of miR-10a-5p in melanoma has not been fully explored. This study aims to confirm LIN28B as the targeted gene of miR-10a-5p which was explored in melanoma cells. In addition, upstream regulatory molecule of miR-10a-5p was also investigated in melanoma cells. Methods Real-time Quantitative polymerase chain reaction (RT-qPCR) was adopted to analyze miR-10a-5p expression level in melanoma and the normal human epidermal melanocyte cells. Several biological assays were performed to evaluate miR-10a-5p influences on cell proliferation, migration and invasion ability in A375 and B16-F10 cells. Gene prediction of miRNA targeting and a dual luciferase assay were applied to assess miR-10a-5p-targeted LIN28B. Western blot assessed the impacts of miR-10a-5p on the protein expression of LIN28B. Western blot analyzed the TCF21 effects on the expression of LIN28B and RT-qPCR assessed the influence of TCF21 on the expression level of miRNA-10a. In addition, Chromatin Immunoprecipitation (ChIP) Assay and JASPAR databases were employed to explore the regulatory relationship between TCF21 and miR-10a-5p. Results We discovered that miR-10a-5p expression was lower in melanoma cells and high expression of miR-10a-5p suppressed the proliferation, migration and invasion abilities of melanoma cells. We also discovered that miR-10a-5p targeted the LIN28B mRNA 3 ' UTR area and diminished LIN28B protein expression. We found that LIN28B expression was strongly decreased by TCF21 upregulation in the two melanoma cells. The qRT-PCR assay showed that miR-10a-5p expression level was obviously boosted by increased TCF21 expression. The results also demonstrated that TCF21 directly regulated miR-10a-5p at transcript levels. Conclusion TCF21 induced miRNA-10a targeting LIN28B could affect the progression and growth of melanoma.

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