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微小RNA-5195-3p通过靶向Toll样受体4/髓样分化因子88信号通路预测临床预后并抑制结直肠癌进展。

MiR-5195-3p predicts clinical prognosis and represses colorectal cancer progression by targeting TLR4/MyD88 signaling.

作者信息

Lv Yandong, Guo Shuwei, Jin Lingtong, Wang Kai, Li Yongsheng, Li Haonan, Lu Yikang, Liu Hongzhou

机构信息

Department of Colorectal Surgery, Heping Hospital Affiliated to Changzhi Medical College, No.110 Yanan South Road, Luzhou District, 046000, Changzhi City, Shanxi Province, P. R. China.

出版信息

Cell Div. 2024 Oct 10;19(1):29. doi: 10.1186/s13008-024-00133-x.

DOI:10.1186/s13008-024-00133-x
PMID:39390599
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11468180/
Abstract

BACKGROUND

Recent studies have highlighted the role of miR-5195-3p in suppressing cell growth in various cancers. However, the specific functional impact of miR-5195-3p in colorectal cancer (CRC) remain to be fully clarified. The importance of miR-5195-3p in CRC was evaluated, aiming to uncover its underlying molecular mechanism and identify it as a potential therapeutic target for CRC.

RESULTS

Our research has shown that miR-5195-3p is markedly under-expressed in CRC tissues and cell cultures, with its reduced presence associated with a higher TNM stage, lymphatic invasion, and unfavorable survival outcome. Ectopic miR-5195-3p expression curtailed proliferation, migration, and invasion of SW1116 and HT29 cells. Additionally, we discovered that miR-5195-3p directly targets and negatively influences Toll-like receptor 4 (TLR4) in CRC cells. Moreover, an inverse relationship was noted between miR-5195-3p and TLR4 expression in CRC tissue samples. Notably, restoring TLR4 expression counteracted miR-5195-3p's suppressive impact on cell growth, motility, invasiveness, epithelial-mesenchymal transition (EMT), and the TLR4/MyD88 signaling pathway in SW1116 and HT29 cells.

CONCLUSIONS

MiR-5195-3p suppresses the CRC cellular functions through the downregulation of TLR4/MyD88 signaling, indicating that targeting miR-5195-3p might offer a viable therapeutic strategy for CRC.

摘要

背景

最近的研究强调了miR - 5195 - 3p在抑制多种癌症细胞生长中的作用。然而,miR - 5195 - 3p在结直肠癌(CRC)中的具体功能影响仍有待充分阐明。本研究评估了miR - 5195 - 3p在CRC中的重要性,旨在揭示其潜在的分子机制,并将其确定为CRC的潜在治疗靶点。

结果

我们的研究表明,miR - 5195 - 3p在CRC组织和细胞培养物中明显低表达,其表达降低与更高的TNM分期、淋巴浸润和不良的生存结果相关。异位表达miR - 5195 - 3p可抑制SW1116和HT29细胞的增殖、迁移和侵袭。此外,我们发现miR - 5195 - 3p直接靶向并负向影响CRC细胞中的Toll样受体4(TLR4)。此外,在CRC组织样本中,miR - 5195 - 3p与TLR4表达之间存在负相关关系。值得注意的是,恢复TLR4表达可抵消miR - 5195 - 3p对SW1116和HT29细胞的细胞生长、运动性、侵袭性、上皮 - 间质转化(EMT)以及TLR4/MyD88信号通路的抑制作用。

结论

MiR - 5195 - 3p通过下调TLR4/MyD88信号传导抑制CRC细胞功能,这表明靶向miR - 5195 - 3p可能为CRC提供一种可行的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea50/11468180/7ca4dde79533/13008_2024_133_Fig6_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea50/11468180/7ca4dde79533/13008_2024_133_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea50/11468180/c401c229d4bc/13008_2024_133_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea50/11468180/9d2b97334920/13008_2024_133_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea50/11468180/cc8ef4bc2109/13008_2024_133_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea50/11468180/b255f2017993/13008_2024_133_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea50/11468180/c9ca4b63b88b/13008_2024_133_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea50/11468180/7ca4dde79533/13008_2024_133_Fig6_HTML.jpg

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本文引用的文献

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The Clinical Significance of MicroRNAs in Colorectal Cancer Signaling Pathways: A Review.微小RNA在结直肠癌信号通路中的临床意义:综述
Glob Med Genet. 2023 Nov 22;10(4):315-323. doi: 10.1055/s-0043-1777094. eCollection 2023 Dec.
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CircRUNX1 drives the malignant phenotypes of lung adenocarcinoma through mediating the miR-5195-3p/HMGB3 network.环状RUNX1通过介导miR-5195-3p/HMGB3网络驱动肺腺癌的恶性表型。
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Snail inhibits metastasis via regulation of E‑cadherin and is associated with prognosis in colorectal cancer.
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MiR-5195-3p functions as a tumor suppressor by targeting RHBDD1 in ovarian cancer.在卵巢癌中,miR-5195-3p通过靶向RHBDD1发挥肿瘤抑制作用。
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The Interaction Between Epigenetic Changes, EMT, and Exosomes in Predicting Metastasis of Colorectal Cancers (CRC).表观遗传变化、上皮-间质转化与外泌体在预测结直肠癌转移中的相互作用
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MiR-5195-3p functions as a tumor suppressor in prostate cancer via targeting CCNL1.miR-5195-3p 通过靶向 CCNL1 在前列腺癌中发挥肿瘤抑制作用。
Cell Mol Biol Lett. 2022 Mar 8;27(1):25. doi: 10.1186/s11658-022-00326-8.
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Screening and prevention of colorectal cancer.结直肠癌的筛查与预防。
BMJ. 2021 Sep 15;374:n1855. doi: 10.1136/bmj.n1855.
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