LINC00461 promotes cell migration and invasion in breast cancer through miR-30a-5p/integrin β3 axis

J Cell Biochem. 2019 Apr;120(4):4851-4862. doi: 10.1002/jcb.27435. Epub 2019 Jan 8.

Abstract

Mounting evidence has demonstrated that long noncoding RNAs (lncRNAs) are dysregulated and implicated in the occurrence and development of a wide range of human malignancies. LINC00461, a novel cancer-related lncRNA, has been reported to be highly expressed and serve as oncogene in glioma; however, its biological role in breast cancer (BC) remains obscure. This study aimed to explore the role of LINC00461 in BC and elucidate the potential molecular mechanisms involved. In the current study, LINC00461 was found to be significantly upregulated in both BC tissues and cell lines. Besides, we found that high LINC00461 expression was associated with TNM stage and differentiation. Furthermore, functional studies demonstrated that LINC00461 expedited BC cell migration and invasion. Notably, LINC00461 was observed to enhance the expression of vimentin and zinc-finger E-box binding homeobox factor 1, suppress the expression of E-cadherin, and promote the activation of extracellular signal-regulated kinase and AKT signaling pathways. Mechanical investigations revealed that LINC00461 positively modulated integrin β3 (ITGB3) expression as miR-30a-5p sponge in BC cells. Taken together, LINC00461 exerts an oncogenic role in BC through miR-30a-5p/ITGB3 axis. Our data indicate that LINC00461 may be used to be a novel candidate therapeutic target and a valuable diagnostic biomarker for BC.

Keywords: LINC00461; breast cancer; integrin β3; miR-30a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Movement*
  • Female
  • Humans
  • Integrin beta3 / genetics
  • Integrin beta3 / metabolism*
  • MCF-7 Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*

Substances

  • ITGB3 protein, human
  • Integrin beta3
  • MIRN30b microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • RNA, Neoplasm