Publication: Up-regulation of oxidized low-density lipoprotein receptor 1 correlates with decreased miR-106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, and miR-4465, higher recurrence rate, and poor prognosis in ovarian cancer
J. Liu, Y. Zeng and L. Zheng
Authors
Liu, Jun ; Zeng, Ya ; Zheng, Lang
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-536
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info:eu-repo/semantics/article
Description
Abstract
. Background. MicroRNAs (miRNAs) are
widely involved in cell metabolism, and their abnormal
expression is involved in the regulation of ovarian
cancer development, metastasis, and recurrence. The
current study aimed to explore the potential mechanism
and prognostic value of miRNAs related to the targeted
regulation of oxidized low-density lipoprotein receptor 1
(OLR1) expression in ovarian cancer.
Methods. A prospective study was conducted
including 132 ovarian cancer patients. Patients were
followed up for 36 months. The dual-luciferase reporter
gene detection was used to verify the targeting
relationship between miRNA and OLR1. Cell Counting
Kit-8 assay, flow cytometric analysis, transwell
migration, and invasion assays were performed to
address the malignant biological behaviors of ovarian
cancer cells.
Results. OLR1 protein and gene expression levels
were significantly higher in ovarian cancer tissues and
cell lines than in adjacent tissues and normal ovarian
epithelial cells. OLR1 depletion facilitated apoptosis and
impeded cell proliferation, migration, and invasion in
ovarian cancer. Predictive software and dual-luciferase
reporter assays showed that miR-106b-5p, miR-93-5p,
miR-3129-5p, miR-199b-3p, and miR-4465 targeted
OLR1 expression. Functionally, the introduction of miR106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, and
miR-4465 mimics abrogated the aggressive phenotype in
ovarian cancer cells. Lastly, compared with adjacent
tissues, the levels of miR-106b-5p, miR-93-5p, miR3129-5p, miR-199b-3p, and miR-4465 in cancer tissues
were significantly lower (P<0.001). Compared with high
miR-106b-5p, high miR-93-5p, high miR-3129-5p, high
miR-199b-3p, high miR-4465 group and low OLR1
group, the low miR-106b-5p, low miR-93-5p, low miR3129-5p, low miR-199b-3p, low miR-4465 group and
high OLR1 group have significantly higher recurrence
(all P<0.05) and higher mortality (all P<0.05). The
identification value of recurrence assessment model [Y =
4.267+0.336*(miR-106b-5p)+0.168*(miR-93-
5p)+1.847*(miR-3129-5p)+2.119*(miR-199b3p)+0.872*(miR-4465)-3.408*(OLR1)] was high with
an AUC of 0.918. The prognosis assessment model [Y =
3.914+0.143*(miR-106b-5p)+0.102*(miR-93-
5p)+0.115*(miR-3129-5p)+1.369*(miR-199b3p)+0.186*(miR-4465)-0.334*(OLR1)] also had high
identification value with an AUC of 0.934.
Conclusion. The combined detection of miR-106b-5p,
miR-93-5p, miR-3129-5p, miR-199b-3p, miR-4465, and
OLR1 is expected to become a molecular biomarker for
the long-term prognostic assessment of ovarian cancer.
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