Let-7c-5p Targeting CHD7 Hinders Cervical Cancer Migration and Invasion by Regulating Cell Adhesion.

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2024-12-16 DOI:10.1007/s10528-024-10993-1
Huichuan Zhao, Lanying Zou, Jun Xu, Xiaoping Zhou, Ya Zhang
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Abstract

Cervical cancer is one of the most common cancers worldwide. Many studies have reported the involvement of various miRNAs in cervical cancer progression. Our study was centered at investigating how let-7c-5p affected cervical cancer migration and invasion by regulating cell adhesion and its molecular mechanism. Bioinformatics was used for the analysis on differentially expressed mRNAs in cervical cancer and the prediction of their upstream regulatory miRNAs. Immunohistochemistry was performed to assess the expression of CHD7 in cervical cancer tissue. qRT-PCR was performed for examining how much let-7c-5p and CHD7 were expressed. Dual-luciferase assay was performed to verify the regulatory relationship between CHD7 and let-7c-5p. The CCK-8 and transwell assays helped in detecting cell viability, invasion and migration. The ability by which cells adhered to each other was detected by employing cell adhesion assay. In addition, the expression levels of the proteins related to cell adhesion and CHD7 were detected by Western blot. A remarkable high expression-level of CHD7 was discovered in cervical cancer tissues and cells. The cell viability, migration and invasiveness could be suppressed by the knockdown of CHD7 which could also attenuate the expression of cell adhesion-related proteins. Bioinformatics analysis showed that CHD7 had an upstream regulatory gene, miRNA-let-7c-5p, which was markedly lowly expressed in cervical cancer tissues and cells. To validate the binding relationship between CHD7 and let-7c-5p, dual-luciferase assay was performed. Rescue experiments revealed that the cancer-inhibiting effect of let-7c-5p in cervical cancer could be reversed by overexpressed CHD7. let-7c-5p regulates cell adhesion and attenuates cervical cancer migration and invasiveness by targeting CHD7. It indicates that the involvement of let-7c-5p/CHD7 axis is of significance in cervical cancer progression, which opens up new possibilities for us to develop novel clinical treatments for cervical cancer.

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靶向CHD7的Let-7c-5p通过调节细胞粘附抑制宫颈癌的迁移和侵袭
子宫颈癌是全球最常见的癌症之一。许多研究报道了各种mirna在宫颈癌进展中的作用。本研究主要探讨let-7c-5p如何通过调控细胞粘附影响宫颈癌的迁移和侵袭及其分子机制。利用生物信息学方法分析宫颈癌中差异表达的mrna,并预测其上游调控mirna。免疫组化检测CHD7在宫颈癌组织中的表达。采用qRT-PCR检测let-7c-5p和CHD7的表达量。双荧光素酶测定验证CHD7和let-7c-5p之间的调控关系。CCK-8和transwell检测有助于检测细胞活力、侵袭和迁移。采用细胞粘附法检测细胞间的相互粘附能力。Western blot检测细胞粘附相关蛋白和CHD7的表达水平。CHD7在宫颈癌组织和细胞中有显著的高表达。敲低CHD7可抑制细胞活力、迁移和侵袭性,并可减弱细胞粘附相关蛋白的表达。生物信息学分析显示,CHD7的上游调控基因miRNA-let-7c-5p在宫颈癌组织和细胞中显著低表达。为了验证CHD7和let-7c-5p之间的结合关系,进行了双荧光素酶测定。挽救实验显示let-7c-5p在宫颈癌中的抑癌作用可被过表达CHD7逆转。let-7c-5p通过靶向CHD7调控细胞粘附,减弱宫颈癌的迁移和侵袭性。提示let-7c-5p/CHD7轴的参与在宫颈癌进展中具有重要意义,这为我们开发新的宫颈癌临床治疗方法开辟了新的可能性。
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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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