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CPNE1 是 miR-335-5p 的靶标,在非小细胞肺癌的发病机制中发挥重要作用。

CPNE1 is a target of miR-335-5p and plays an important role in the pathogenesis of non-small cell lung cancer.

机构信息

Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Suzhou Key Laboratory for Respiratory Diseases, Suzhou, 215006, China.

出版信息

J Exp Clin Cancer Res. 2018 Jul 3;37(1):131. doi: 10.1186/s13046-018-0811-6.

DOI:10.1186/s13046-018-0811-6
PMID:29970127
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6029376/
Abstract

BACKGROUND

Despite advances in diagnosis and treatment, the survival of non-small cell lung cancer (NSCLC) patients remains poor. There is therefore a strong need to identify potential molecular targets for the treatment of NSCLC. In the present study, we investigated the function of CPNE1 in the regulation of cell growth, migration and invasion.

METHODS

Quantitative real-time PCR (qRT-PCR) was used to detect the expression of CPNE1 and miR-335-5p. Western blot and immunohistochemical assays were used to investigate the levels of CPNE1 and other proteins. Flow cytometry was used to determine cell cycle stage and apoptosis. CCK-8 and clonogenic assays were used to investigate cell proliferation. Wound healing, migration and invasion assays were used to investigate the motility of cells. A lung carcinoma xenograft mouse model was used to investigate the in vivo effects of CPNE1 overexpression.

RESULTS

We observed that knockdown of CPNE1 and increased expression of miR-335-5p inhibits cell proliferation and motility in NSCLC cells, and found that CPNE1 was a target of miR-335-5p. In addition, our data indicated that CPNE1 inhibition could improve the clinical effects of EGFR-tyrosine kinase inhibitors.

CONCLUSIONS

The present results indicate that CPNE1 may be a promising molecular target in the treatment of NSCLC.

摘要

背景

尽管在诊断和治疗方面取得了进展,但非小细胞肺癌(NSCLC)患者的生存率仍然较低。因此,强烈需要确定治疗 NSCLC 的潜在分子靶标。在本研究中,我们研究了 CPNE1 在调节细胞生长、迁移和侵袭中的功能。

方法

使用实时定量 PCR(qRT-PCR)检测 CPNE1 和 miR-335-5p 的表达。使用 Western blot 和免疫组织化学检测 CPNE1 和其他蛋白质的水平。使用流式细胞术确定细胞周期阶段和细胞凋亡。使用 CCK-8 和集落形成测定法研究细胞增殖。使用划痕愈合、迁移和侵袭测定法研究细胞的运动性。使用肺癌异种移植小鼠模型研究 CPNE1 过表达的体内效应。

结果

我们观察到 CPNE1 敲低和 miR-335-5p 表达增加抑制 NSCLC 细胞的增殖和迁移,并且发现 CPNE1 是 miR-335-5p 的靶标。此外,我们的数据表明 CPNE1 抑制可以改善 EGFR 酪氨酸激酶抑制剂的临床效果。

结论

本研究结果表明,CPNE1 可能是治疗 NSCLC 的有前途的分子靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/24a37d055a6a/13046_2018_811_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/4beb3ccd7c82/13046_2018_811_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/84e317252794/13046_2018_811_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/abd182020796/13046_2018_811_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/b6b0905a3dff/13046_2018_811_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/906a072ab819/13046_2018_811_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/e6238ad76583/13046_2018_811_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/24a37d055a6a/13046_2018_811_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/4beb3ccd7c82/13046_2018_811_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/84e317252794/13046_2018_811_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/abd182020796/13046_2018_811_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/b6b0905a3dff/13046_2018_811_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/906a072ab819/13046_2018_811_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/e6238ad76583/13046_2018_811_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8729/6029376/24a37d055a6a/13046_2018_811_Fig7_HTML.jpg

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