miR-29b-3p inhibits 22Rv1 prostate cancer cell proliferation through the YWHAE/BCL-2 regulatory axis.

miR-29b-3p inhibits 22Rv1 prostate cancer cell proliferation through the YWHAE/BCL-2 regulatory axis.
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miR‐29b‐3p 通过 YWHAE/BCL‐2 调控轴抑制 22Rv1 前列腺癌细胞增殖

DOI:
10.3892/ol.2022.13409
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发表时间:
2022-08
期刊:
影响因子:
2.9
通讯作者:
--
中科院分区:
医学4区
文献类型:
--
作者:

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前列腺癌是世界上最常见的恶性肿瘤之一,严重影响男性健康。研究表明microRNA(miR)-29 b-3 p和酪氨酸3-单加氧酶/色氨酸5-单加氧酶激活蛋白(YWHAE)在影响PCa细胞增殖和凋亡中起重要作用。然而,miR-29 b-3 p和YWHAE在PCa细胞增殖和凋亡中的分子机制尚不清楚。本研究采用生物信息学方法,结合体内外实验,预测并验证YWHAE与mir-29 b-3 p的靶向性关系,探讨YWHAE与mir-29 b-3 p在22 RV 1细胞增殖和凋亡中的作用。利用生物信息学和双荧光素酶系统分析证实,miR-29 b-3 p可以靶向YWHAE 3′非翻译区,影响YWHAE的表达,提示miR-29 b-3 p可能是YWHAE潜在的miRNA。RT-PCR、Cell Counting Kit-8、Transwell和细胞划痕实验显示,miR-29 b-3 p对22 Rv 1细胞的增殖、侵袭和迁移能力均有明显抑制作用(P<0. 01)。挽救实验表明,YWHAE基因导入逆转了miR-29 b-3 p对22 Rv 1细胞的抑制作用。Western blotting结果显示,miR-29 b-3 p的上调抑制了YWHAE的表达,导致p-BAD/BAD和全长caspase 3/cleaved caspase 3的比值非常显著地降低(P<0.01),BAX/BCL-2的比值非常显著地升高(P<0.01)。裸鼠体内肿瘤发生试验证实,miR-29 b-3 p的上调通过靶向YWHAE抑制肿瘤生长。本实验证实miR-29 b-3 p在22 Rv 1 PCa细胞中具有抑癌作用,YWHAE/BCL-2调控轴在miR-29 b-3 p调控22 Rv 1细胞增殖和凋亡中起重要作用。这些结果可能为PCa的诊断和靶向治疗提供理论依据。
Prostate cancer (PCa) is one of the most common malignant tumours in the world and seriously affects health of men. Studies have shown that microRNA (miR)-29b-3p and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (YWHAE) play important roles in influencing the proliferation and apoptosis of PCa cells. However, the molecular mechanism of miR-29b-3p and YWHAE in the proliferation and apoptosis of PCa cells remains unclear. In the present study, bioinformatics as well as in vivo and in vitro experiments were used to predict and verify the targeting relationship between YWHAE and mir-29B-3p and investigate the potential roles of YWHAE and mir-29b-3p in the proliferation and apoptosis of 22RV1 cells. Using bioinformatics and a double luciferase system assay, it was confirmed that miR-29b-3p can target YWHAE 3′untranslated region and affect the expression of YWHAE, suggesting that miR-29b-3p may be a potential miRNA of YWHAE. Reverse transcription-quantitative PCR, Cell Counting Kit-8, Transwell and cell scratch assays showed that miR-29b-3p significantly inhibited the proliferation, invasion and migration of 22Rv1 cells (P<0.01). Rescue experiments demonstrated that YWHAE gene introduction reversed the inhibitory effect of miR-29b-3p on 22Rv1 cells. Western blotting revealed that the upregulation of miR-29b-3p inhibited YWHAE expression, resulting in a very significant decrease in the ratio of p-BAD/BAD and full-length caspase 3/cleaved caspase 3 (P<0.01) and an extremely significant increase in the ratio of BAX/BCL-2 (P<0.01). A tumourigenesis test in nude mice in vivo confirmed that the upregulation of miR-29b-3p inhibited tumour growth by targeting YWHAE. The present experiments confirmed that miR-29b-3p plays a tumour suppressor role in 22Rv1 PCa cells, and the YWHAE/BCL-2 regulatory axis plays a vital role in miR-29b-3p regulating the proliferation and apoptosis of 22Rv1 cells. These results may provide a theoretical basis for the diagnosis and targeted treatment of PCa.
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发表时间: 2015-08
期刊: Annals of oncology : official journal of the European Society for Medical Oncology
影响因子: --
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发表时间: 2020
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发表时间: 2012-05-01
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影响因子: 7.5
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