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miR-377通过与BCL-2/Bax、PTEN和CDK4相互作用调节MYC mRNA,从而对前列腺癌细胞的增殖和侵袭行为产生抑制作用。

Inhibitory effect of miR-377 on the proliferative and invasive behaviors of prostate cancer cells through the modulation of MYC mRNA via its interaction with BCL-2/Bax, PTEN, and CDK4.

作者信息

Azimi Yasamin, Hajibabaei Sara, Azimi Ghazal, Rahimi-Jamnani Fatemeh, Azizi Masoumeh

机构信息

Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Department of Nanotechnology, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.

出版信息

Genes Cancer. 2024 May 16;15:28-40. doi: 10.18632/genesandcancer.236. eCollection 2024.

DOI:10.18632/genesandcancer.236
PMID:38756697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11098572/
Abstract

The MYC gene is a regulatory and proto-oncogenic gene that is overexpressed in the majority of prostate cancers (PCa). Numerous studies have indicated that aberrant expression of microRNAs is involved in the initiation and progression of prostate cancer. In this investigation, we assessed the impact of miR-377 on MYC through luciferase assay. Real-time PCR was employed to determine whether miR-377 could reduce the levels of MYC mRNA in transfected PCa cell lines (PC-3 and DU145) and change in the mRNA levels of BCL-2/Bax, PTEN, and CDK4 as a consequence of MYC downregulation. Moreover, we analyzed the effects of miR-377 on apoptosis, proliferation, cell cycle, and wound healing. Our findings demonstrate that miR-377 effectively targets MYC mRNA, as confirmed by luciferase assay and Real-time PCR. We observed a significant reduction in BCL-2 and CDK4 expression, along with an increase in Bax and PTEN, in prostate cancer cell lines upon MYC suppression. Additionally, elevated levels of miR-377 in PCa cell lines induced apoptosis, inhibited proliferation and migration, and arrested the cell cycle. Taken together, these results unveil the inhibitory role of miR-377 in MYC function within PCa, thereby suggesting its potential as a therapeutic target for the treatment of this malignancy.

摘要

MYC基因是一种调控性原癌基因,在大多数前列腺癌(PCa)中过度表达。大量研究表明,微小RNA的异常表达与前列腺癌的发生和发展有关。在本研究中,我们通过荧光素酶测定评估了miR-377对MYC的影响。采用实时PCR来确定miR-377是否能降低转染的前列腺癌细胞系(PC-3和DU145)中MYC mRNA的水平,以及由于MYC下调导致的BCL-2/Bax、PTEN和CDK4 mRNA水平的变化。此外,我们分析了miR-377对细胞凋亡、增殖、细胞周期和伤口愈合的影响。我们的研究结果表明,荧光素酶测定和实时PCR证实miR-377有效地靶向MYC mRNA。我们观察到在前列腺癌细胞系中,抑制MYC后,BCL-2和CDK4表达显著降低,同时Bax和PTEN增加。此外,前列腺癌细胞系中miR-377水平升高可诱导细胞凋亡、抑制增殖和迁移,并使细胞周期停滞。综上所述,这些结果揭示了miR-377在前列腺癌中对MYC功能的抑制作用,从而表明其作为治疗这种恶性肿瘤的潜在治疗靶点的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/60f56ebd68b3/ganc-15-236-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/78970a914e61/ganc-15-236-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/e385965077a0/ganc-15-236-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/cf8d5648233e/ganc-15-236-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/2a0b9838065c/ganc-15-236-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/60f56ebd68b3/ganc-15-236-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/78970a914e61/ganc-15-236-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/e385965077a0/ganc-15-236-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/cf8d5648233e/ganc-15-236-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/2a0b9838065c/ganc-15-236-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d9/11098572/60f56ebd68b3/ganc-15-236-g005.jpg

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本文引用的文献

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CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis.环状 RNA 血管生成素 A 通过调控 miR-377-3p 和 miR-494-3p/IGF1R/AKT 轴促进小细胞肺癌进展。
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MYC drives aggressive prostate cancer by disrupting transcriptional pause release at androgen receptor targets.MYC 通过扰乱雄激素受体靶基因的转录暂停释放来驱动侵袭性前列腺癌。
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