Upregulated lncRNA-UCA1 contributes to metastasis of bile duct carcinoma through regulation of miR-122/CLIC1and activation of the ERK/MAPK signaling pathway
Autor: | Lei Kong, Huali Yang, Liangchao Zhao, Jinhua Ye, Qinghua Wu, Nengping Li |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
MAPK/ERK pathway medicine.diagnostic_test Cell Cell migration Cell Biology Biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Downregulation and upregulation Western blot 030220 oncology & carcinogenesis microRNA Cancer research medicine MiR-122 Signal transduction Molecular Biology Developmental Biology |
Zdroj: | Cell Cycle. 18:1212-1228 |
ISSN: | 1551-4005 1538-4101 |
DOI: | 10.1080/15384101.2019.1593647 |
Popis: | In the present study, we aimed to identify specific lncRNAs and miRNAs, as well as mRNAs, involved in bile duct carcinoma (BDC) and to further explore the way in which lncRNA UCA1 regulates cell metastasis ability. Differentially expressed RNAs were screened out from the TCGA database. In in vitro experiments, qRT-PCR was used to measure lncRNA UCA1, miR-122 and CLIC1 expression. We performed a dual luciferase assay to validate the target relationships among UCA1, CLIC1 and miR-122. The cell migration ability was measured by a wound healing assay, and Transwell assays were applied to detect cell invasive ability. Western blot analysis was employed to detect the expression of related proteins in the MAPK signaling pathway. According to the bioinformatics analysis, lncRNA UCA1 and CLIC1 were both significantly upregulated in BDC, while the expression of miR-122 declined compared with the normal group. The target relationship among UCA1, CLIC1 and miR-122 was verified. UCA1 promoted BDC cell migration and invasiveness, while miR-122 inhibited their progression. CLIC1 served as the downstream target gene of miR-122 and had opposite effects. The ERK/MAPK signaling pathway was activated after upregulating UCA1. LncRNA-UCA1 promoted the metastasis of BDC cells by regulating the expression of miR-122 and its downstream gene mRNA CLIC1 and promoted the activation of the ERK/MAPK pathway, which expanded the horizons of targeted therapy of cholangiocarcinoma. |
Databáze: | OpenAIRE |
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