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

In Vitro Cell Dev Biol Anim. 2019 Jun;55(6):426-435. doi: 10.1007/s11626-019-00361-4. Epub 2019 May 28.

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.

Keywords: Breast cancer; FBXL19-AS1; LIN28A; Tumor progression; WDR66.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Calcium-Binding Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Oncogenes
  • RNA Stability
  • RNA, Antisense
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism

Substances

  • Calcium-Binding Proteins
  • LIN28B protein, human
  • RNA, Antisense
  • RNA-Binding Proteins
  • WDR66 protein, human