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Hsa-miR-125b在结肠癌中的治疗作用取决于TP53基因的突变状态。

Hsa-miR-125b Therapeutic Role in Colon Cancer Is Dependent on the Mutation Status of the TP53 Gene.

作者信息

Cenariu Diana, Zimta Alina-Andreea, Munteanu Raluca, Onaciu Anca, Moldovan Cristian Silviu, Jurj Ancuta, Raduly Lajos, Moldovan Alin, Florea Adrian, Budisan Liviuta, Pop Laura Ancuta, Magdo Lorand, Albu Mihai Tudor, Tonea Rares Bogdan, Muresan Mihai-Stefan, Ionescu Calin, Petrut Bogdan, Buiga Rares, Irimie Alexandru, Gulei Diana, Berindan-Neagoe Ioana

机构信息

MEDFUTURE-Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street/Louis Pasteur 4-6 Street, 400337 Cluj-Napoca, Romania.

Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania.

出版信息

Pharmaceutics. 2021 May 6;13(5):664. doi: 10.3390/pharmaceutics13050664.

DOI:10.3390/pharmaceutics13050664
PMID:34066331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8148199/
Abstract

Colon cancer is the third most common cancer type worldwide and is highly dependent on DNA mutations that progressively appear and accumulate in the normal colon epithelium. Mutations in the gene appear in approximately half of these patients and have significant implications in disease progression and response to therapy. miR-125b-5p is a controversial microRNA with a dual role in cancer that has been reported to target specifically in colon adenocarcinomas. Our study investigated the differential therapeutic effect of miR-125b-5p replacement in colon cancer based on the mutation status of colon cancer cell lines. In mutated models, miR-125b-5p overexpression slows cancer cells' malignant behavior by inhibiting the invasion/migration and colony formation capacity via direct downregulation of mutated . In wild type cells, the exogenous modulation of miR-125b-5p did not significantly affect the molecular and phenotypic profile. In conclusion, our data show that miR-125b-5p has an anti-cancer effect only in mutated colon cancer cells, explaining partially the dual behavior of this microRNA in malignant pathologies.

摘要

结肠癌是全球第三大常见癌症类型,高度依赖于在正常结肠上皮细胞中逐渐出现和积累的DNA突变。约半数此类患者会出现该基因的突变,这对疾病进展和治疗反应具有重要影响。miR-125b-5p是一种具有争议性的微小RNA,在癌症中具有双重作用,据报道它在结肠腺癌中特异性靶向。我们的研究基于结肠癌细胞系的突变状态,调查了miR-125b-5p替代疗法在结肠癌中的差异治疗效果。在突变模型中,miR-125b-5p过表达通过直接下调突变体来抑制侵袭/迁移和集落形成能力,从而减缓癌细胞的恶性行为。在野生型细胞中,miR-125b-5p的外源性调节对分子和表型特征没有显著影响。总之,我们的数据表明,miR-125b-5p仅在突变的结肠癌细胞中具有抗癌作用,这部分解释了这种微小RNA在恶性病变中的双重行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/400a7b9fc75b/pharmaceutics-13-00664-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/d361838f36f6/pharmaceutics-13-00664-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/76bc4664fdbe/pharmaceutics-13-00664-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/273b8e3159d4/pharmaceutics-13-00664-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/f4f10ab591d1/pharmaceutics-13-00664-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/400a7b9fc75b/pharmaceutics-13-00664-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/d361838f36f6/pharmaceutics-13-00664-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/76bc4664fdbe/pharmaceutics-13-00664-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/273b8e3159d4/pharmaceutics-13-00664-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/f4f10ab591d1/pharmaceutics-13-00664-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c197/8148199/400a7b9fc75b/pharmaceutics-13-00664-g007.jpg

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Modified TLR-mediated downregulation of miR-125b-5p enhances CD248 (endosialin)-induced metastasis and drug resistance in colorectal cancer cells.
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