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Down-regulated long non-coding RNA RNAZFHX4-AS1 suppresses invasion and migration of breast cancer cells via FAT4-dependent Hippo signaling pathway

Cancer Gene Therapy volume 26, pages 374–387 (2019)Cite this article

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Abstract

Breast cancer is ranked as the second leading cause of cancer-related deaths among women. Accumulating evidences have revealed that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis owing to the regulation of essential pathways for tumor initiation and progression. Herein, the current study aimed to explore the regulatory mechanism of lncRNA ZFHX4-AS1 in breast cancer in relation to the Hippo signaling pathway. Initially, microarray analysis was conducted to screen out differentially expressed lncRNAs related to breast cancer. Next, the functional role of lncRNA ZFHX4-AS1 in breast cancer was determined using ectopic expression, knockdown, and reporter assay experiments. Subsequently, lncRNA ZFHX4-AS1, TAF4, TAZ, and YAP expressions were determined, followed by verification of the targeting relationship between lncRNA ZFHX4-AS1 and TAF4. Then cell proliferation, invasion, migration, cell cycle, and apoptosis were measured. Lastly, tumor growth and metastasis were detected by tumor xenograft in nude mice. LncRNA ZFHX4-AS1 was found to be highly expressed while FAT4 was poorly expressed in breast cancer tissues. FAT4 was the target gene of lncRNA ZFHX4-AS1, and lncRNA ZFHX4-AS1 silencing increased FAT4 expressions, while decreased YAP and TAZ expressions. In addition, knockdown of lncRNA ZFHX4-AS1 suppressed breast cancer cell proliferation, migration, and invasion as well as tumor growth, blocked cell cycle entry, while promoted cell apoptosis by inhibiting the Hippo signaling pathway. In conclusion, our findings reveal that lncRNA ZFHX4-AS1 silencing exerts an inhibitory effect on breast cancer development by suppressing the activation of the Hippo signaling pathway via FAT4.

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Acknowledgements

We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.

Authors’ contributions

S-YL and HW designed the study. S-YL, HW, H-FM, G-FL., and S-JC collated the data, designed, and developed the database, carried out data analyses, and produced the initial draft of the manuscript. H-FM, S-JC, G-SL, and B-CL contributed to drafting the manuscript. All authors participated in editing and revising the manuscript and have read and approved the final submitted manuscript.

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Authors and Affiliations

  1. Department of Thyroid and Breast Surgery, Baoan Maternal and Child Health Hospital, Jinan University, Sanming Project of Medicine in Shenzhen, 518000, Shenzhen, P.R. China

    Shao-Ying Li, Hui-Fang Mai, Gui-Sen Li & Bi-Chan Liang

  2. Department of Breast Surgery, Zhuhai Maternity and Child Health Hospital, 519001, Zhuhai, P.R. China

    Hong Wang

  3. Department of Thoracic Surgery, Shenzhen People’s Hospital, 518000, Shenzhen, P.R. China

    Guo-Feng Li

  4. Department of Breast Surgery, Shenzhen Maternity and Child Health Hospital, 518000, Shenzhen, P.R. China

    Shao-Jun Chen

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  1. Shao-Ying Li
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Correspondence to Shao-Ying Li.

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The authors declare that they have no conflict of interest.

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Collection of specimens and clinical data were approved by the Moral and Ethical Committee of Baoan Maternal and Child Health Hospital, Jinan University, Sanming Project of Medicine in Shenzhen. Signed informed consents were obtained from all patients and their families before collecting the specimens. All animal experiments were in line with the social guidelines of the China Animal Ethics Committee, and all efforts were made to minimize the suffering of the included animals.

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Li, SY., Wang, H., Mai, HF. et al. Down-regulated long non-coding RNA RNAZFHX4-AS1 suppresses invasion and migration of breast cancer cells via FAT4-dependent Hippo signaling pathway. Cancer Gene Ther 26, 374–387 (2019). https://doi.org/10.1038/s41417-018-0066-6

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