Institute of Bioinformatics and Applied Biotechnology, Bangalore, India.
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, USA.
Cancer Rep (Hoboken). 2022 Oct;5(10):e1596. doi: 10.1002/cnr2.1596. Epub 2022 Jan 4.
Curcumin is well known for its anticancer properties. Its cytotoxic activity has been documented in several cancer cell lines, including breast cancer. The pleiotropic activity of curcumin as an antioxidant, an antiangiogenic, antiproliferative, and pro-apoptotic, is due to its diverse targets, such as signaling pathways, protein/enzyme, or noncoding gene.
This study aimed to identify key miRNAs and mRNAs induced by curcumin in breast cancer cells MCF7, T47D (hormone positive), versus MDA-MB231 (hormone negative) using comparative analysis of global gene expression profiles.
RNA was isolated and subjected to mRNA and miRNA library sequencing to study the global gene expression profile of curcumin-treated breast cancer cells. The differential expression of gene and miRNA was performed using the DESeq R package. The enriched pathways were studied using cluster profileR, and integrated miRNA-mRNA analysis was carried out using miRtarvis and miRmapper tools.
Curcumin treatment led to upregulation of 59% TSGs in MCF7, 21% in MDA-MB-231 cells, and 36% TSGs in T47D, and downregulation of 57% oncogenes in MCF7, 76% in MDA-MB-231, and 91% in T47D. Similarly, curcumin treatment led to upregulation of 32% TSmiRs in MCF7, 37.5% in MDA-MB231, and 62.5% in T47D, and downregulation of 77% oncomiRs in MCF7, 50% in MDA-MB231 and 28.6% in T47D. Integrated analysis of miRNA-mRNA led to the identification of a common NFKB pathway altered by curcumin in all three cell lines. Analysis of uniquely enriched pathway revealed non-integrin membrane-ECM interactions and laminin interactions in MCF7; extracellular matrix organization and degradation in MDA-MB-231 and cell cycle arrest and G2/M transition in T47D.
Curcumin regulates miRNA and mRNA in a cell type-specific manner. The integrative analysis led to the detection of miRNAs and mRNAs pairs, which can be used as biomarkers associated with carcinogenesis, diagnostic, and treatment response in breast cancer.
姜黄素以其抗癌特性而闻名。其细胞毒性已在多种癌细胞系中得到证实，包括乳腺癌。姜黄素作为抗氧化剂、抗血管生成、抗增殖和促凋亡的多效活性归因于其多样化的靶点，如信号通路、蛋白质/酶或非编码基因。
本研究旨在使用比较分析全局基因表达谱，鉴定姜黄素在乳腺癌细胞 MCF7、T47D（激素阳性）与 MDA-MB231（激素阴性）中诱导的关键 miRNA 和 mRNA。
提取 RNA，进行 mRNA 和 miRNA 文库测序，研究姜黄素处理后的乳腺癌细胞的全局基因表达谱。使用 DESeq R 包进行基因和 miRNA 的差异表达分析。使用 cluster profileR 研究富集途径，并使用 miRtarvis 和 miRmapper 工具进行 miRNA-mRNA 综合分析。
姜黄素处理导致 MCF7 中 59%的 TSGs 上调，MDA-MB-231 中 21%的 TSGs 上调，T47D 中 36%的 TSGs 上调，MCF7 中 57%的癌基因下调，MDA-MB-231 中 76%的癌基因下调，T47D 中 91%的癌基因下调。同样，姜黄素处理导致 MCF7 中 32%的 TSmiRs 上调，MDA-MB231 中 37.5%的 TSmiRs 上调，T47D 中 62.5%的 TSmiRs 上调，MCF7 中 77%的 oncomiRs 下调，MDA-MB-231 中 50%的 oncomiRs 下调，T47D 中 28.6%的 oncomiRs 下调。miRNA-mRNA 的综合分析导致鉴定出 NFKB 途径在所有三种细胞系中均受姜黄素改变。对独特富集途径的分析显示 MCF7 中存在非整联蛋白膜-ECM 相互作用和层粘连蛋白相互作用；MDA-MB-231 中存在细胞外基质组织和降解；T47D 中存在细胞周期停滞和 G2/M 转变。
姜黄素以细胞类型特异性方式调节 miRNA 和 mRNA。综合分析导致检测到 miRNA 和 mRNA 对，可作为与乳腺癌发生、诊断和治疗反应相关的生物标志物。
