miR-1204 Positioning in 8q24.21 Involved in the Tumorigenesis of Colorectal Cancer by Targeting MASPIN.

IF 1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Protein and Peptide Letters Pub Date : 2024-01-01 DOI:10.2174/0109298665305114240718072029
Simeng Tian, Meilin Chen, Wanting Jing, Qinghui Meng, Jie Wu
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Abstract

Background: Colorectal cancer remains to be the third leading cause of cancer mortality rates. Despite the diverse effects of the miRNA cluster located in PVT1 of 8q24.21 across various tumors, the specific biological function in colorectal cancer has not been clarified.

Methods: The amplification of the miR-1204 cluster was analyzed with the cBioPortal database, while the expression and survival analysis of the miRNAs in the cluster were obtained from several GEO databases of colorectal cancer. To investigate the functional role of miR-1204 in colorectal cancer, overexpression and silencing experiments were performed by miR-1204 mimic and inhibitor transfection in colorectal cancer cell lines, respectively. Then, the effects of miR-1204 on cell proliferation were assessed through CCK-8, colony formation, and Edu assay. In addition, cell migration was evaluated using wound healing and Transwell assay. Moreover, candidate genes identified through RNA sequencing and predicted databases were identified and validated using PCR and western blot. A Dual-luciferase reporter experiment was conducted to identify MASPIN as the target gene of miR-1204.

Results: In colorectal cancer, the miR-1204 cluster exhibited high amplification, and the expression levels of several cluster miRNAs were also significantly increased. Furthermore, miR-1204 was found to be significantly associated with disease-specific survival according to the analysis of GSE17536. Functional experiments demonstrated that transfection of miR-1204 mimic or inhibitor could enhance or decrease cancer cell proliferation and migration. MASPIN was identified as a target of miR-1204. Additionally, the overexpression of MASPIN partially rescued the effect of miR-1204 mimics on tumorigenic abilities in LOVO cells.

Conclusion: miR-1204 positioning in 8q24.21 promotes the proliferation and migration of colorectal cancer cells by targeting MASPIN.

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miR-1204 在 8q24.21 中的定位通过靶向 MASPIN 参与结直肠癌的肿瘤发生
背景:结直肠癌仍然是癌症死亡率的第三大原因。尽管位于 8q24.21 PVT1 的 miRNA 簇在各种肿瘤中的作用各不相同,但其在结直肠癌中的具体生物学功能尚未明确:方法:利用 cBioPortal 数据库分析了 miR-1204 簇的扩增情况,同时从多个结直肠癌 GEO 数据库中获得了该簇中 miRNA 的表达和生存分析。为了研究 miR-1204 在结直肠癌中的功能作用,研究人员分别用 miR-1204 模拟物和抑制剂转染结直肠癌细胞系,进行了过表达和沉默实验。然后,通过 CCK-8、菌落形成和 Edu 试验评估了 miR-1204 对细胞增殖的影响。此外,还利用伤口愈合和 Transwell 试验评估了细胞迁移。此外,通过 RNA 测序和预测数据库确定了候选基因,并使用 PCR 和 Western 印迹进行了验证。通过双荧光素酶报告实验确定了 MASPIN 为 miR-1204 的靶基因:结果:在结直肠癌中,miR-1204集群表现出高度扩增,几个集群miRNA的表达水平也显著增加。此外,根据 GSE17536 的分析发现,miR-1204 与疾病特异性生存显著相关。功能实验证明,转染 miR-1204 模拟物或抑制剂可增强或降低癌细胞的增殖和迁移。MASPIN被确定为miR-1204的靶点。结论:位于 8q24.21 的 miR-1204 通过靶向 MASPIN 促进结直肠癌细胞的增殖和迁移。
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来源期刊
Protein and Peptide Letters
Protein and Peptide Letters 生物-生化与分子生物学
CiteScore
2.90
自引率
0.00%
发文量
98
审稿时长
2 months
期刊介绍: Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis
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