| 常征张爱民郝俊文△ 徐友和刘毅.miR-221 通过作用DVL2 影响前列腺癌细胞系的侵袭功能*[J].,2012,12(15):2881-2886 |
| miR-221 通过作用DVL2 影响前列腺癌细胞系的侵袭功能* |
| MiR-221 Expression Affects Invasion Potential of Human ProstateCarcinoma Cell Lines by Regulating DVL2* |
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| DOI： |
| 中文关键词: 前列腺癌 miR-22 DVL2 神经元特异性烯醇酶 |
| 英文关键词: Prostate cancer MiR-221 DVL2 NSE |
| 基金项目:第二军医大学博士创新基金 |
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| 中文摘要: |
| 目的：评价miR-221 在前列腺癌细胞系中表达的变化对其神经内分泌样转化及其侵袭功能的影响。方法：以Northern blot
检测LNCaP，LNCaP-AI 两种前列腺癌细胞系中7 种microRNA 的表达变化；细胞转染法检测在雄激素剥夺环境中LNCaP 和
LNCaP-AI 细胞系中miR-221 的作用；CCK-8 法检测细胞在不同阶段的生长增殖水平；Transwell 法检测转染细胞的侵袭能力；
qRT-PCR 和Western blot 检测转染的细胞中神经元特异性烯醇化酶（NSE）及dishevelled-2（DVL2）表达的变化。结果：与雄激素
依赖性前列腺癌（ADPC）的细胞系LNCaP 相比，miR-221 在雄激素非依赖性前列腺癌（AIPC）的细胞系LNCaP-AI 中明显高表达。
通过转染使miR-221 在LNCaP 细胞系中高表达可促进细胞的NSE 表达，加速其神经内分泌样分化。而在LNCaP-AI 细胞系中下
调miR-221 水平则会升高靶基因DVL2 的表达水平，并增强LNCaP-AI 细胞的迁移和侵袭能力。结论：该实验证实在AIPC 和
ADPC 细胞系中miR-221 存在表达差异。miR-221 可促进前列腺癌细胞的神经内分泌样转化，这可能是导致前列腺癌雄激素非依
赖转化的重要原因。MiR-221 可通过作用DVL2 调节晚期前列腺癌细胞的转移和侵袭。 |
| 英文摘要: |
| Objective: To investigate the effect of miR-221 on the neuroendocrine （NE）differentiation and invasive function of
prostate cancer cells as a miRNA biomarker candidate for prostate cancer. Methods: The expressions of 7 miRNAs in LNCaP, LNCaP-AI
prostate cancer cell lines were detected by Northern blotting. LNCaP and LNCaP-AI cells cultured in androgen-depleted medium were
transfected with different synthetic miRNAs. Their invasive abilities were evaluated by a matrigel invasion assay. Cell growth was
assessed by using the CCK-8 cell proliferation assay at different time points. The expression of neuron-specific enolase （NSE ）and
Dishevelled-2 （DVL2）during the neuroendocrine differentiation and migration respectively were measured by qRT-PCR and Western
blot. Results: The miR-221 level increased significantly in androgen-independent prostate cancer (AIPC) cell line LNCaP-AI when
compared with androgen-dependent prostate cancer (ADPC) cell line LNCaP. Overexpression of miR-221 in LNCaP cells increased
significantly NSE expression and induced their NE differentiation. The suppression of miR-221 expression with anti-miR-221 increased
the abilities of migration and invasion in LNCaP-AI cells. Meanwhile, the DVL2 mRNA and protein levels were upregulated after the
transfection of anti-miR-221 in LNCaP-AI cells. Conclusions: There is a significant difference for miR-221 expression between ADPC
and AIPC cells. MiR-221 contributes to NE differentiation of ADPC cells, which may be the reason of androgen-independence. miR-221
may regulate the migration of AIPC cells through DVL2 as a key regulator in advanced prostate cancer. |
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