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Cyclooxygenase-2, a Potential Therapeutic Target, Is Regulated by miR-101 in Esophageal Squamous Cell Carcinoma.
- Source :
-
PloS one [PLoS One] 2015 Nov 10; Vol. 10 (11), pp. e0140642. Date of Electronic Publication: 2015 Nov 10 (Print Publication: 2015). - Publication Year :
- 2015
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Abstract
- Background & Aims: Cyclooxygenase-2 (COX-2) is known to promote the carcinogenesis of esophageal squamous cell carcinoma (ESCC). There are no reports on whether microRNAs (miRNAs) regulate COX-2 expression in ESCC. This study investigated the effect of miR-101 on ESCC through modulating COX-2 expression in ESCC.<br />Methods: Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify miR-101 expression in ESCC clinical tissues and cell lines. The effects of miR-101 on ESCC progression were evaluated by cell counting kit-8 (CCK8), transwell migration and invasion assays, as well as by flow cytometry. The COX-2 and PEG2 levels were determined by western blot and enzyme-linked immunosorbent assays (ELISA). The luciferase reporter assay was used to verify COX-2 as a direct target of miR-101. The anti-tumor activity of miR-101 in vivo was investigated in a xenograft nude mouse model of ESCC.<br />Results: Downregulation of miR-101 was confirmed through comparison of 30 pairs of ESCC tumor and adjacent normal tissues (P < 0.001), as well as in 11 ESCC cell lines and a human immortalized esophageal cell line (P < 0.001). Transfection of miR-101 in ESCC cell lines significantly suppressed cell proliferation, migration, and invasion (all P < 0.001). The antitumor effect of miR-101 was verified in a xenograft model. Furthermore, COX-2 was shown to be a target of miR-101.<br />Conclusions: Overexpression of miR-101 in ESCC inhibits proliferation and metastasis. Therefore, the miR-101/COX-2 pathway might be a therapeutic target in ESCC.
- Subjects :
- Animals
Carcinoma, Squamous Cell genetics
Carcinoma, Squamous Cell therapy
Cell Line, Tumor
Cell Movement
Cyclooxygenase 2 genetics
Down-Regulation
Enzyme Induction genetics
Esophageal Neoplasms genetics
Esophageal Neoplasms therapy
Esophagus chemistry
Gene Expression Regulation, Neoplastic genetics
Genes, Reporter
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs biosynthesis
Molecular Targeted Therapy
Neoplasm Invasiveness
Neoplasm Proteins genetics
RNA, Neoplasm biosynthesis
Real-Time Polymerase Chain Reaction
Transfection
Xenograft Model Antitumor Assays
Carcinoma, Squamous Cell enzymology
Cyclooxygenase 2 biosynthesis
Esophageal Neoplasms enzymology
Genetic Therapy
MicroRNAs genetics
Neoplasm Proteins biosynthesis
RNA, Neoplasm genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26556718
- Full Text :
- https://doi.org/10.1371/journal.pone.0140642