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基于生物信息学探究 has_circ_RBMS3 在乳腺癌骨转移中的作用及潜在机制。

To investigate the role and potential mechanism of has_circ_RBMS3 in bone metastasis of breast cancer based on bioinformatics.

机构信息

Department of Outpatient, West China Hospital, Sichuan University, Chengdu, Sichuan, 610044, China.

West China School of Nursing, Sichuan University, Chengdu, Sichuan, 610044, China.

出版信息

Cell Biochem Biophys. 2024 Sep;82(3):2227-2236. doi: 10.1007/s12013-024-01332-7. Epub 2024 Jun 1.

Abstract

Circular RNAs (circRNAs) play a crucial regulatory role in malignant tumor metastasis. This study focused on the role of bone metastasis-related circRBMS3 in breast cancer. Two circRNA microarray datasets were obtained from the GEO database and overlapped bone metastasis-related circRNAs in breast cancer. CircRBMS3 expression was validated in bone metastasis tissues by RT-qPCR. Cellular CCK-8 assay and Transwell assays were performed to measure the effect of circRBMS3 in breast cancer cells. Bioinformatic analyses were performed to identify the binding miRNAs of circRBMS3 and downstream mRNAs. Online database STRING and Cytoscape software were used to analyze PPI interaction and conduct the ceRNA network. GEO database analysis showed that circRBMS3 was one of the upregulated circRNAs among all the metastatic cells. CircRBMS3 was increased in bone metastasis breast cancer tissues compared to non-bone metastasis tissues and associated with poor 3-year overall survival. CircRBMS3 knockdown repressed breast cancer cell proliferation, migration, and invasion, as well as bone resorption gene and osteoclast phenotype gene expression. CircRBMS3 was found to bind withmiR-654-3p. Subsequently, downstream mRNAs were predicted, and the circRBMS3 miR-654-3p-mRNA network was established. In conclusion, circRBMS3 expression was upregulated in bone metastasis breast cancer and might be a potential prognostic marker for patients. Silencing circRBMS3 restrained breast cancer cell proliferation, migration, and invasion, as well as associated with bone metastasis. The circRBMS3-miR-654-3p-mRNAs network elucidated potential mechanisms underlying bone metastasis in breast cancer.

摘要

环状 RNA(circRNAs)在恶性肿瘤转移中发挥着关键的调控作用。本研究聚焦于乳腺癌骨转移相关环状 RNA RBMS3(circRBMS3)的作用。从 GEO 数据库中获取了两个环状 RNA 微阵列数据集,并对乳腺癌中与骨转移相关的环状 RNA 进行了重叠分析。通过 RT-qPCR 验证了骨转移组织中 circRBMS3 的表达。通过细胞 CCK-8 测定和 Transwell 测定来测量 circRBMS3 对乳腺癌细胞的影响。进行了生物信息学分析以鉴定 circRBMS3 的结合 miRNA 和下游 mRNAs。使用在线数据库 STRING 和 Cytoscape 软件分析 PPI 相互作用并构建 ceRNA 网络。GEO 数据库分析表明,circRBMS3 是所有转移性细胞中上调的环状 RNA 之一。与非骨转移组织相比,骨转移乳腺癌组织中 circRBMS3 增加,并且与 3 年总生存率不良相关。circRBMS3 敲低抑制乳腺癌细胞增殖、迁移和侵袭,以及骨吸收基因和破骨细胞表型基因的表达。发现 circRBMS3 与 miR-654-3p 结合。随后,预测下游 mRNAs,并建立了 circRBMS3-miR-654-3p-mRNA 网络。总之,circRBMS3 在骨转移乳腺癌中表达上调,可能是患者的潜在预后标志物。沉默 circRBMS3 可抑制乳腺癌细胞的增殖、迁移和侵袭,并与骨转移有关。circRBMS3-miR-654-3p-mRNAs 网络阐明了乳腺癌骨转移的潜在机制。

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