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Abstract：
Circular RNAs (circRNAs) are a new group of endogenous RNAs recently found to be involved in the development of various diseases, including their confirmed involvement in the progression of several types of cancers. Unluckily, the abnormal expression and functions of circRNAs in breast cancer shall be further investigated. This work aims to elucidate the action and molecular mechanism of circHSDL2 in the malignant progression of breast cancer. Differential expression profiles of circRNAs in breast cancer tissues relative to normal breast tissues and in the exosomes of breast cancer patients compared to healthy women were analyzed from databases to identify potentially functional circRNAs. CircHSDL2 was selected for further investigation. Cell proliferation, migration and invasion assays were done to assess the effect of circHSDL2 overexpression on breast cancer cells. Bioinformatics test and dual-luciferase reporter experiments were done to explore the interaction between circHSDL2 and miRNA. Downstream target genes were further investigated through proteomics analysis and Western blotting. The influence of circHSDL2 on breast cancer in vivo was evaluated through xenograft experiments in nude mice. Functional analysis demonstrated circHSDL2 overexpression promoted the division, movement, and invasion of breast cancer cells both in vivo and in vitro. Mechanistically, circHSDL2 acted as a sponge for miR-7978 to affect ZNF704 expression and thereby regulate the Hippo pathway in breast cancer cells. In conclusion, circHSDL2 regulates the Hippo pathway through the miR-7978/ZNF704 axis to facilitate the malignancy of breast cancer. This may be a potential biomarker and treatment target.
摘要：
环状RNA（circularRNAs，circRNAs）是最近发现的一类新的内源性RNA，与各种疾病的发展有关。包括他们证实参与几种癌症的进展。不幸的是,circRNAs在乳腺癌中的异常表达和功能有待进一步研究。本文旨在阐明circHSDL2在乳腺癌恶性进展中的作用及其分子机制。从数据库中分析了circRNAs在乳腺癌组织中相对于正常乳腺组织和乳腺癌患者外泌体中相对于健康女性的差异表达谱，以鉴定潜在的功能性circRNAs。选择CircHSDL2进行进一步研究。细胞增殖，进行迁移和侵袭分析以评估circHSDL2过表达对乳腺癌细胞的影响。进行生物信息学测试和双荧光素酶报告基因实验以探索circHSDL2与miRNA之间的相互作用。通过蛋白质组学分析和蛋白质印迹进一步研究下游靶基因。通过裸鼠异种移植实验评估circHSDL2对体内乳腺癌的影响。功能分析显示circHSDL2过表达促进了分裂，运动,和乳腺癌细胞在体内和体外的侵袭。机械上,circHSDL2充当miR-7978的海绵，影响ZNF704的表达，从而调节乳腺癌细胞中的Hippo途径。总之,circHSDL2通过miR-7978/ZNF704轴调节Hippo途径以促进乳腺癌的恶性。这可能是潜在的生物标志物和治疗靶标。
