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HSP90AA1-mediated autophagy promotes drug resistance in osteosarcoma

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, August 2018
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Title
HSP90AA1-mediated autophagy promotes drug resistance in osteosarcoma
Published in
Journal of Experimental & Clinical Cancer Research, August 2018
DOI 10.1186/s13046-018-0880-6
Pubmed ID
Authors

Xin Xiao, Wei Wang, Yuqian Li, Di Yang, Xiaokang Li, Chao Shen, Yan Liu, Xianzhu Ke, Shuo Guo, Zheng Guo

Abstract

Osteosarcoma is the most common primary bone tumor in children and adolescents. Unfortunately, osteosarcoma treatments often fail due to the development of chemoresistance, of which the underlying molecular mechanisms still remain unclear. In this study, we demonstrated that HSP90AA1 gene is responsible for drug resistance in osteosarcoma through an autophagy-related mechanism. shRNAs were transfected into osteosarcoma cells for knockdown of HSP90AA1 gene. Stable HSP90AA1 overexpressing osteosarcoma cell lines were obtained by lentivirus infection. mRNA and protein expressions of HSP90AA1 in osteosarcoma cells were tested by quantitative real-time PCR and western blot, respectively. Autophagy of osteosarcoma cells was detected by western blot of LC3, transmission electron microscopy and fluorescence microscope. mRFP-GFP-LC3 lentiviral transfection was also performed to detect autophagic flux. NOD/SCID mices were inoculated with MG-63 tumor cells transfected with HSP90AA1 specific shRNA. TUNEL and LC3 staining were performed to detect apoptosis and autophagy of resected tumor tissues. Doxorubicin, cisplatin, and methotrexate, which are commonly used in chemotherapy, each induced HSP90AA1 upregulation in human osteosarcoma cells. Suppression of HSP90AA1 restored the sensitivity of osteosarcoma cells to chemotherapy both in vivo and in vitro. Mechanism study indicated that autophagy is responsible for the chemoresistance in osteosarcoma cells. HSP90AA1 increased drug resistance by inducing autophagy and inhibiting apoptosis. Suppression of HSP90AA1 diminished autophagic protection in response to chemotherapy in osteosarcoma cells. Moreover, HSP90AA1 promotes autophagy through PI3K/Akt/mTOR pathway and inhibits apoptosis through JNK/P38 pathway. We showed that chemotherapy agents can induce HSP90AA1 expression in osteosarcoma cells. And HSP90AA1, acting as an important regulator of autophagy, is a critical factor in the development of osteosarcoma chemoresistance both in vitro and in vivo. HSP90AA1 provides a novel therapeutic target for improving osteosarcoma treatment.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 119 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 119 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 17%
Student > Master 15 13%
Student > Doctoral Student 9 8%
Student > Bachelor 9 8%
Researcher 6 5%
Other 11 9%
Unknown 49 41%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 32 27%
Medicine and Dentistry 12 10%
Agricultural and Biological Sciences 5 4%
Pharmacology, Toxicology and Pharmaceutical Science 5 4%
Neuroscience 3 3%
Other 9 8%
Unknown 53 45%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 August 2018.
All research outputs
#22,767,715
of 25,385,509 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#1,970
of 2,382 outputs
Outputs of similar age
#301,280
of 344,178 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#57
of 72 outputs
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So far Altmetric has tracked 2,382 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 72 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.