Dataset Information

MicroRNA?590 inhibits migration, invasion and epithelial?to?mesenchymal transition of esophageal squamous cell carcinoma by targeting low?density lipoprotein receptor?related protein 6.

ABSTRACT: MicroRNA?590 (miR?590) has been revealed as a tumor suppressor, while low?density lipoprotein receptor?related protein 6 (LRP6) is considered to act as a tumor promoter. However, their roles and underlying molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC) have yet to be fully elucidated. Therefore, the present study aimed to investigate these mechanisms. The expression levels of miR?590 and LRP6 in human ESCC samples and cell lines were determined using reverse transcription?quantitative PCR. Bioinformatics analysis was used to predict the relationship between miR?590 and LRP6, and luciferase assay was performed to validate the relationship between these factors. Transwell assays were used to determine cell migration and invasion, while western blotting assays were used to detect the protein expression levels of LRP6, E?cadherin, N?cadherin and Vimentin. The present study demonstrated that miR?590 was downregulated and LRP6 was upregulated in ESCC tissues and cell lines. Furthermore, it was found that miR?590 overexpression and LRP6 knockdown inhibited cell migration, invasion and epithelial?to?mesenchymal transition (EMT) in ESCC cell lines. Additional mechanistic studies identified that LRP6 was a target of, and was inhibited by, miR?590. Collectively, the present findings suggested that miR?590 inhibited the invasion, migration and EMT of ESCC cells by mediating LRP6.

SUBMITTER: Guan H

PROVIDER: S-EPMC7448422 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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MicroRNA‑590 inhibits migration, invasion and epithelial‑to‑mesenchymal transition of esophageal squamous cell carcinoma by targeting low‑density lipoprotein receptor‑related protein 6.

Guan Hongya H Liu Jia J Lv Pengju P Zhou Lijuan L Zhang Jianying J Cao Wei W

Oncology reports 20200715 4

MicroRNA‑590 (miR‑590) has been revealed as a tumor suppressor, while low‑density lipoprotein receptor‑related protein 6 (LRP6) is considered to act as a tumor promoter. However, their roles and underlying molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC) have yet to be fully elucidated. Therefore, the present study aimed to investigate these mechanisms. The expression levels of miR‑590 and LRP6 in human ESCC samples and cell lines were determined using reverse transcr ...[more]

PMID: 32945478

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Project description:Esophageal squamous cell carcinoma (ESCC) is a malignant disease with poor prognosis. Because of early metastasis prior to diagnosis and therapeutic resistance, ESCC has become one of the leading causes of cancer-related death. Here, we investigated the clinicopathological significance of the association of octamer-binding transcription factor 4 (OCT4) with lymphoid enhancer-binding factor 1 (LEF1) expression and the potential molecular mechanism in the epithelial-mesenchymal transition (EMT), invasion, and migration of ESCC. The expression of OCT4 and LEF1 was detected via immunohistochemistry analysis. High levels of LEF1 expression were observed in 95 ESCC specimens and were obviously associated with aberrant clinicopathological features and poor patient prognosis. Our previous study showed that OCT4 expression level is elevated in ESCC, and statistical analysis showed that the elevated expression of OCT4 and LEF1 in ESCC was significantly associated with histologic grade, lymph node metastasis, TNM stage, and poor patient prognosis. The specific inhibition of OCT4 expression via a lentivirus encoding OCT4-shRNA (LV-shOCT4) in Eca109 cells led to decreased levels of OCT4 and LEF1 in vitro. Additionally, we applied a rescue strategy by infecting LV-shOCT4 Eca109 cells with a LEF1 overexpression plasmid (p-LEF1) and detected changes in EMT, migration, and invasion. Unsurprisingly, the p-LEF1 group exhibited greater EMT, invasion, and migration than did the LV-shOCT4 and negative control groups. This study demonstrates for the first time the relationship between OCT4 and LEF1 expression. The combination of high expression of OCT4 and LEF1 was associated with clinicopathological features of atypical patients, and this combination might be an ideal prognostic factor in ESCC. OCT4 positively regulated LEF1 expression, and LEF1 mediated the effects of OCT4 in cancer cell EMT, invasion, and migration. The data presented here suggest that the inhibition of OCT4-LEF1 signaling may be a new therapeutic target for the treatment of ESCC.

Project description:PurposeHepatocellular carcinoma (HCC) is a highly aggressive malignant tumor, the prognosis of which remains poor. Recently, microRNAs have been reported to play crucial functions in multiple tumors, including HCC. However, the molecular mechanisms of miR-370 in HCC still remain largely unknown. The present study focused on the effects of miR-370 on HCC migration, invasion, and epithelial-mesenchymal transition (EMT).Materials and methodsWe investigated the key roles and possible regulatory mechanism of miR-370 in regulating HCC metastasis with functional assays, such as transwell assay. Quantitative real-time PCR (qRT-PCR) was used to detect miR-370 and guanylylcyclase domain containing 1 (GUCD1) expression in HCC tissues and cells. Subsequently, we performed transwell assays to determine the functions of miR-370 in HCC cell invasion and migration. Western blot was used to determine protein expressions of relevant genes. Luciferase reporter assays were conducted to confirm the target gene of miR-370.ResultsqRT-PCR analysis demonstrated that miR-370 was dramatically downregulated in HCC. Moreover, downregulated miR-370 was found to be associated with poor survival and adverse clinicopathologic characteristics of HCC patients. Transwell assays revealed that miR-370 overexpression dramatically suppressed HCC invasion and migration. Meanwhile, miR-370 restoration prominently inhibited EMT progression in HCC cells. Luciferase reporter assays confirmed GUCD1 as a downstream target gene of miR-370. GUCD1 expression in HCC tissues was prominently increased and inversely correlated with miR-370 expression. Furthermore, GUCD1 was verified as mediating the suppressive influence of miR-370 on cell metastasis and EMT in HCC.ConclusionTaken together, our study confirmed that miR-370 suppressed HCC cell metastasis and EMT via regulating GUCD1. Accordingly, the miR-370/GUCD1 axis may potentially acts as attractive therapeutic targets and novel biomarkers for HCC treatment.

Dataset Information

MicroRNA?590 inhibits migration, invasion and epithelial?to?mesenchymal transition of esophageal squamous cell carcinoma by targeting low?density lipoprotein receptor?related protein 6.

Publications

MicroRNA‑590 inhibits migration, invasion and epithelial‑to‑mesenchymal transition of esophageal squamous cell carcinoma by targeting low‑density lipoprotein receptor‑related protein 6.

Similar Datasets

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