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Plasma exosome-derived miR-20a-5p affects bone metastasis in estrogen receptor-positive breast cancer cells by targeting PIK3R1 / 中华内分泌外科杂志
Chinese Journal of Endocrine Surgery ; (6): 485-491, 2022.
Article in Chinese | WPRIM | ID: wpr-954624
ABSTRACT

Objective:

To investigate the effects of plasma exosome-derived miR-20a-5p on bone metastases in estrogen receptor-positive breast cancer (ER (+) BC) by targeting PIK3R1.

Methods:

The data sets related to ER (+) BC bone metastasis were retrieved with the help of bioinformatics website, miR-20a-5p was included in the study. The plasma of 90 ER (+) BC patients and the corresponding healthy people were collected to detect the expression of PIK3R1 in the plasma, and exosomes were extracted from the plasma to detect expression of miR-20a-5p in exosomes. The dual-luciferase reporter assay was used to verify the targeting regulation relationship between miR-20a-5p and PIK3R1. The exosomes transfected with NC-inhibitor and miR-inhibitor or ER (+) BC cells transfected with si-NC and si-PIK3R1 were injected into the left ventricle of mice, respectively, and the bone tissue was scanned by Micro-CT and bone tissue TRAP staining was performed. After co-culturing NC-inhibitor and miR-inhibitor-transfected exosomes with si-NC and si-PIK3R1-transfected ER (+) BC cells, Western blot was used to detect the expression of osteoclast molecules c-fos and NFATc1.

Results:

qRT-PCR assay showed that compared with normal plasma exosomes (1±0.26) or cells (1±0.13) , miR-20a-5p was significantly increased in ER (+) BC plasma exosomes (1.49±0.27) ( t=12.40, P<0.001) and BC cell line MCF-7 (1.64±0.13) ( t=6.03, P=0.004) , BT474 (1.49±0.11) ( t=4.98, P=0.008) , T47D (1.98±0.15) ( t=8.55, P=0.001) . But compared with normal plasma exosomes (1±0.25) or cells (1±0.10) , expression of PIK3R1 in ER (+) BC plasma exosomes (0.69±0.24) ( t=8.48, P<0.001) and ER (+) BC cell lines MCF-7 (0.73±0.05) ( t=4.18, P=0.014) , BT474 (0.61±0.05) ( t=6.04, P=0.004) , and T47D (0.34±0.04) ( t=10.61, P<0.001) was inhibited. PIK3R1 was confirmed as a target gene of miR-20a-5p. Compared with mice in NC-inhibitor group, trabecular bone tissue volume ( t=3.32, P=0.029) , trabecular bone area volume ( t=6.24, P=0.003) , bone volume fraction ( t=7.35, P=0.002) and bone mineral density ( t=13.72, P<0.001) of mice in miR-inhibitor group were both increased, the number of mature osteoclasts was decreased. Compared with NC inhibitor group, expression of c-fos ( t=9.04, P=0.001) and NFATc1 ( t=13.42, P<0.001) in miR-inhibitor group was decreased. Compared with miR-inhibitor+si-NC group, trabecular bone tissue volume ( t=3.03, P=0.039) , trabecular bone area volume ( t=6.37, P=0.003) , bone volume fraction ( t=3.36, P=0.028) and bone mineral density ( t=6.92, P=0.002) were decreased, the number of mature osteoclasts was increased, and expressionof c-fos ( t=7.75, P= 0.002) and NFATc1 ( t=9.65, P=0.001) was increased in miR-inhibitor+si-PIK3R1 group.

Conclusion:

PlasmaExosome-derived miR-20a-5p from ER (+) BC patients promotes ER (+) BC bone metastasis by inhibiting the expression of PIK3R1.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Endocrine Surgery Year: 2022 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Endocrine Surgery Year: 2022 Type: Article