Over-Expressed miR-224 Promotes the Progression of Cervical Cancer via Targeting RASSF8

Cervical cancer is the most common cause of cancer-related deaths in women from developing countries. Identification of novel prognostic predictors or therapeutic targets may improve patient prognosis. In the current study, we demonstrated by real-time PCR that miR-224 expression was significantly u...

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Bibliographic Details
Published in:PloS one 2016-09, Vol.11 (9), p.e0162378-e0162378
Main Authors: Huang, YongJie, Li, Yang, Wang, Fen F, Lv, WeiGuo, Xie, Xing, Cheng, Xiaodong
Format: Article
Language:English
Subjects:
Adult
Biology and life sciences
Cancer
Cancer metastasis
Cell Line, Tumor
Cell migration
Cell Proliferation
Cervical cancer
Cervix
Chemotherapy
Colorectal cancer
Comparative analysis
Developing countries
Development and progression
Disease Progression
Ethics
Female
Genomes
Health aspects
Humans
LDCs
Li, Yang
Luciferase
Lung cancer
Medical prognosis
Medical research
Medicine
Medicine and Health Sciences
Metastases
MicroRNAs
MicroRNAs - genetics
Oncology
Prognosis
Research and Analysis Methods
RNA-mediated interference
Tissues
Tumor cell lines
Tumor Suppressor Proteins - genetics
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - pathology
Womens health
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Summary:Cervical cancer is the most common cause of cancer-related deaths in women from developing countries. Identification of novel prognostic predictors or therapeutic targets may improve patient prognosis. In the current study, we demonstrated by real-time PCR that miR-224 expression was significantly upregulated (1.82-fold, P = 0.0025) in cervical cancer tissues (n = 126) compared with in normal cervical tissues (n = 64). Higher expression of miR-224 was significantly associated with poorer prognostic factors, including advanced FIGO stage, nodal metastasis, larger tumor size, vascular involvement and deep stromal invasion (all P < 0.05). Enforced expression of miR-224 promoted cell proliferation, migration and invasion in SiHa and CaSki cancer cell lines. Bioinformatic analysis indicated that RASSF8 (RAS-association domain family 8) was a potential target of miR-224. Western blot analysis and luciferase reporter assay showed that overexpressed miR-224 inhibited RASSF8 protein expression and decreased the activity of a luciferase reporter containing the 3' untranslated region (UTR) of RASSF8, respectively. Further, RASSF8 knockdown by specific RNAi showed similar effects in cervical cancer cells transfected with miR-224 mimic. Our findings suggest that miR-224 directly targets RASSF8 and thereby acts as a tumor promoter in cervical cancer progression.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0162378