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MicroRNA let-7g acts as tumor suppressor and predictive biomarker for chemoresistance in human epithelial ovarian cancer
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Remarkable deregulation of microRNAs has been demonstrated in epithelial ovarian cancer (EOC). In particular, some of the let-7 miRNA family members have been proposed as tumor suppressors. Here, we explored the functional roles of let-7g in EOC. The ectopic overexpression of let-7g in OVCAR3 and HEY-A8 EOC cells induced i) a down-regulation of c-Myc and cyclin-D2 thus promoting cell cycle arrest, ii) a reduction of Vimentin, Snail and Slug thus counteracting the progression of epithelial to mesenchymal transition, iii) a chemosensitization to cis-platinum treatment. Next, analysis of human EOC tissues revealed that let-7g expression was significantly reduced in tumor tissue specimens of patients with EOC compared to their non-tumor counterparts (p = 0.0002). Notably, low let-7g tissue levels were significantly associated with acquired chemoresistance of patients with late-stage of EOC (n = 17, p = 0.03194). This finding was further validated in the serum samples collected from the same cohort of patients (n = 17, p = 0.003). To conclude, we demonstrate that let-7g acts as tumor suppressor and might be used to disable EOC tumor progression and chemoresistance to cis-platinum-based chemotherapy. Furthermore, we propose that decreased expression of let-7g could serve as a tissue and serum biomarker able to predict the chemo-resistant features of EOC patients.
- Subjects :
- 0301 basic medicine
Epithelial-Mesenchymal Transition
Cell cycle checkpoint
endocrine system diseases
Down-Regulation
lcsh:Medicine
Apoptosis
Vimentin
Carcinoma, Ovarian Epithelial
Article
law.invention
03 medical and health sciences
0302 clinical medicine
law
Cell Line, Tumor
microRNA
Biomarkers, Tumor
Carcinoma
medicine
Humans
Genes, Tumor Suppressor
Neoplasms, Glandular and Epithelial
Epithelial–mesenchymal transition
lcsh:Science
Cell Proliferation
Ovarian Neoplasms
Regulation of gene expression
Multidisciplinary
biology
business.industry
lcsh:R
Middle Aged
medicine.disease
female genital diseases and pregnancy complications
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
Drug Resistance, Neoplasm
Tumor progression
biology.protein
Cancer research
Suppressor
Female
lcsh:Q
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....26915867e4fdeb2c6aad193b716e0859