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New application of miR-154-5p in prostate cancer bone metastasis

A technology for prostate cancer and bone metastasis, applied in the field of biomedicine, can solve the unreported clinical significance and biological effects of miR-154-5p, and achieve the effect of inhibiting bone metastasis

Active Publication Date: 2020-02-21
THE SECOND AFFILIATED HOSPITAL OF GUANGZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the clinical significance and biological role of miR-154-5p in PCa bone metastasis, as well as the underlying molecular mechanism by which miR-154-5p regulates PCa bone metastasis have not been reported

Method used

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  • New application of miR-154-5p in prostate cancer bone metastasis
  • New application of miR-154-5p in prostate cancer bone metastasis
  • New application of miR-154-5p in prostate cancer bone metastasis

Examples

Experimental program
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Effect test

Embodiment 1

[0072] Example 1, miR-154-5p down-regulated expression in prostate cancer with bone metastases

[0073] By analyzing 29 PCa tissues with bone metastasis (PCa / BM) and 163 PCa tissues without bone metastasis (PCa / nBM), such as figure 1 As shown, we found that the expression level of miR-154-5p was significantly downregulated in PCa / BM compared with PCa / nBM. At the cellular level in vitro, such as figure 2 As shown, the expression levels of miR-154-5p in the other 6 PCa cells were significantly down-regulated compared with RWPE-1. It can be seen that miR-154-5p is down-regulated in prostate cancer with bone metastasis.

Embodiment 2

[0074] Example 2. Low level of miR-154-5p predicts shorter bone metastasis-free survival in prostate cancer patients

[0075] Kaplan-Meier survival analysis shows that if image 3 showed that compared with patients with high miR-154-5p expression, PCa patients with low miR-154-5p expression were associated with shorter bone metastasis-free survival, but had no effect on overall survival. It can be seen that low miR-154-5p expression 154-5p can predict shorter bone metastasis-free survival in prostate cancer patients, that is, a high propensity for bone metastasis.

Embodiment 3

[0076] Example 3. Up-regulation of miR-154-5p inhibits bone metastasis of PCa in vivo

[0077] The effect of miR-154-5p on bone metastasis in PCa was further investigated in a mouse bone metastasis model in which PCa were inoculated with a luciferase-labeled vector or PCa transfected with an overexpressing miR-154-5p vector. -3 cells, detection of bone metastases such as Figure 4 As shown, BLI and X-ray showed that compared with the vehicle control group, miR-154-5p significantly inhibited the bone metastatic ability of PC-3 cells in vivo, and H&E staining showed that upregulation of miR-154-5p could significantly reduce Tumor burden in bone. Moreover, upregulation of miR-154-5p expression decreased the bone metastasis score and osteolytic area of ​​metastatic tumors and prolonged overall and bone metastasis-free survival compared with the vehicle control group. These findings suggest that upregulation of miR-154-5p suppresses bone metastasis of PCa in vivo.

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Abstract

The invention finds down-regulation expression of miR-154-5p in prostate cancer bone metastasis tissue for the first time, and the down-regulation expression of the miR-154-5p can predict that the lifetime without bone metastasis is relatively short. In-vivo and in-vitro research further determines that up-regulation of the miR-154-5p inhibits bone metastasis of PCa in vivo, and up-regulation of the miR-154-5p inhibits migration, invasion and proliferation of PCa cells. Based on the result, the invention provides a new application of the miR-154-5p in bone metastasis of prostate cancer.

Description

technical field [0001] The invention belongs to the field of biomedicine, and more specifically relates to miR-154-5p, a biomarker for prostate cancer bone metastasis. Background technique [0002] The most preferential metastatic site of prostate cancer (PCa) is the bone, with an incidence as high as 65%–80% in patients with advanced PCa. Once cancer cells spread to the bone, they wreak havoc on normal bone remodeling, leading to fractures, nerve compression, pain and hypercalcemia. Although great progress has been made in the treatment of primary PCa in the past few decades, distant bone metastasis is still the main problem leading to the short survival time of PCa patients. Compared with primary PCa patients, the 5-year relative survival rate of PCa patients with distant bone metastatic sites is approximately 30%. Prevention of bone metastasis is the main goal of treatment, and it is crucial to elucidate key factors or verify the molecular mechanism of PCa's high propen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886A61K45/00A61P35/04
CPCC12Q1/6886A61K45/00A61P35/04C12Q2600/158C12Q2600/118C12Q2600/178Y02A50/30
Inventor 黄帅廖壮文林卓远王斌钟少文
Owner THE SECOND AFFILIATED HOSPITAL OF GUANGZHOU MEDICAL UNIV
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