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LIN28A-stabilized FBXL19-AS1 promotes breast cancer migration, invasion and EMT by regulating WDR66

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Abstract

Breast cancer ranks as the top reason for the oncologic mortality for female around the world. The occurrence rate of breast cancer is rapidly rising, especially in China. Although the therapeutic regimes for breast cancer are diverse, the treatment outcome in patients remains dismal. Long non-coding RNAs have been greatly reported as important participators in cancer progression during the past decades. FBXL19 antisense RNA 1 (FBXL19-AS1) has been identified as a novel oncogene in colorectal cancer recently, but its role in breast cancer remains unknown. Present study attempted to explore the functional role and mechanism of FBXL19-AS1 in breast cancer progression. Expression of FBXL19-AS1, lin-28 homolog A (LIN28A), and WD repeat domain 66 (WDR66) were detected by qPCR and Western blotting. Transwell assay was used to detect cell migration and invasion. RIP assay was used to examine interaction between LIN28A and FBXL19-AS1. First, FBXL19-AS1 was highly expressed in breast cancer cell lines. Loss-of-function assays indicated that FBXL19-AS1 promoted cell migration, invasion, and EMT in breast cancer. Mechanistically, FBXL19-AS1 interacted with and was stabilized by LIN28A, an RNA-binding protein which has been reported to be able to stabilize lncRNAs. Moreover, WDR66 expression was promoted by FBXL19-AS1 at mRNA and protein level. Finally, rescue assays suggested that FBXL19-AS1 promoted migration, invasion, and EMT through regulating WDR66 in breast cancer. Current study proved that LIN28A-stabilized FBXL19-AS1 promoted breast cancer metastasis by regulating WDR66, identifying FBXL19-AS1 as a new biological marker in breast cancer.

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Acknowledgements

The authors sincerely appreciate all members contributed to this work.

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Authors and Affiliations

  1. Department of Thyroid and Breast Surgery, Shenzhen People’s Hospital, 2nd Clinical Medical College, Jinan University, 1017 North of Dongmen Road, Luohu District, Shenzhen, 518020, Guangdong Province, China

    Yayuan Zhang, Wenbing Zhou & Dongxian Zhou

  2. Ultrasonography Department, Shenzhen People’s Hospital, 2nd Clinical Medical College, Jinan University, Shenzhen, 518020, Guangdong Province, China

    Xiaojun Xiao

  3. Department of Pathology, Shenzhen People’s Hospital, 2nd Clinical Medical College, Jinan University, Shenzhen, 518020, Guangdong Province, China

    Jintao Hu

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  1. Yayuan Zhang
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  2. Xiaojun Xiao
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  3. Wenbing Zhou
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  5. Dongxian Zhou
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Correspondence to Dongxian Zhou.

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Editor: Tersuji Okamoto

Yayuan Zhang and Xiaojun Xiao are co-first author

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Supplementary Figure 1

A Results of qPCR confirmed the overexpression of FBXL19-AS1 by pcDNA3.1/FBXL19-AS1 in BT474 and MDA-MB-231 cells. B–C Transwell assay showed that cell migration and invasion were enhanced by FBXL19-AS1 overexpression. D Western blot assay showed that E-cadherin level was decreased, whereas N-cadherin and Vimentin levels were increased by FBXL19-AS1 overexpression. E The 13 RNA-binding proteins predicted to interact with FBXL19-AS1 in Starbase. *P < 0.05, **P < 0.01, ***P < 0.001. (PNG 676 kb)

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Zhang, Y., Xiao, X., Zhou, W. et al. LIN28A-stabilized FBXL19-AS1 promotes breast cancer migration, invasion and EMT by regulating WDR66. In Vitro Cell.Dev.Biol.-Animal 55, 426–435 (2019). https://doi.org/10.1007/s11626-019-00361-4

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  • DOI: https://doi.org/10.1007/s11626-019-00361-4

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