ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2

Autor: Shuai Diao, Xingwei Jiang, Huan Wu, Hongtao Zhu, Jianguo Hu, Xiaoling Gan
Rok vydání: 2019
Předmět:
0301 basic medicine
Cancer Research
Carcinoma
Ovarian Epithelial
medicine.disease_cause
Mice
0302 clinical medicine
Nude mouse
Cell Movement
biology
AlkB Homolog 5
RNA Demethylase
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Immunohistochemistry
ErbB Receptors
Gene Expression Regulation
Neoplastic
Proto-Oncogene Proteins c-bcl-2
Oncology
030220 oncology & carcinogenesis
Heterografts
Beclin-1
Female
RNA Interference
Signal transduction
Adult
BCL-2
lcsh:RC254-282
03 medical and health sciences
Cell Line
Tumor
Autophagy
medicine
Animals
Humans
Gene silencing
Beclin1
Aged
Cell Proliferation
Neoplasm Staging
Oncogene
Cell growth
Research
DNA Methylation
ALKBH5
biology.organism_classification
medicine.disease
Disease Models
Animal
MicroRNAs
030104 developmental biology
Cancer research
Ectopic expression
Neoplasm Grading
miR-7
EGFR
Carcinogenesis
Ovarian cancer
Zdroj: Journal of Experimental & Clinical Cancer Research : CR
Journal of Experimental & Clinical Cancer Research, Vol 38, Iss 1, Pp 1-15 (2019)
ISSN: 1756-9966
DOI: 10.1186/s13046-019-1159-2
Popis: Background ALKBH5 regulated the malignant behavior of breast cancer and glioblastoma. However, the expression and function of ALKBH5 in epithelial ovarian cancer have not yet been determined. In the present study, we investigated the expression and function of ALKBH5 in epithelial ovarian cancer with respect to its potential role in the tumorigenesis of the disease as well as an early diagnostic marker. Methods Immunohistochemistry and western blot were used to detect protein expression. Gene silencing and over-expression experiment were used to study gene function. Cell proliferation assay and Matrigel invasion assays were used to detect cell proliferation and invasion, respectively. The nude mouse tumor formation experiment was used to evaluate the growth of cells in vivo. Results The expression of ALKBH5 was found to be increased in epithelial ovarian cancer tissue as compared to the normal ovarian tissues. The silencing of ALKBH5 in SKOV3 cells enhanced the autophagy and inhibited the proliferation and invasion in vitro and in vivo, whereas the ectopic expression of ALKBH5 in A2780 cells exerted an opposite effect. Mechanical study revealed that ALKBH5 physically interacted with HuR. ALKBH5 activated EGFR-PIK3CA-AKT-mTOR signaling pathway. Also, ALKBH5 enhanced the stability of BCL-2 mRNA and promoted the interaction between Bcl-2 and Beclin1. Conclusion Overall, the present study identified ALKBH5 as a candidate oncogene in epithelial ovarian cancer and a potential target for ovarian cancer therapy. Electronic supplementary material The online version of this article (10.1186/s13046-019-1159-2) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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