Long non-coding RNA LINC00968 reduces cell proliferation and migration and angiogenesis in breast cancer through up-regulation of PROX1 by reducing hsa-miR-423-5p

Cell Cycle. 2019 Aug;18(16):1908-1924. doi: 10.1080/15384101.2019.1632641. Epub 2019 Jun 29.

Abstract

Background: Breast cancer (BC) is a common invasive malignancy in women with unclear etiology. A recent study suggested that long non-coding RNA (lncRNA), LINC00968 had a tumor-promoting effect in cancer. However, the role of LINC00968 in BC remains unclear. Therefore, we conducted the present study to determine the effect of LINC00968 in BC and its underlying mechanism. Methods: The expression of LINC00968 and hsa-miR-423-5p in BC tissues and cells was determined using reverse transcription quantitative polymerase chain reaction and western blot analysis. Dual luciferase reporter, RNA pull-down and RNA immunoprecipitation assays were used to determine the relationship among LINC00968, PROX1 and hsa-miR-423-5p. Gain- and loss-function approaches were utilized to examine the effects of LINC00968, PROX1 and hsa-miR-423-5p on cell proliferation, migration, tube formation in vitro; and tumor growth and angiogenesis in vivo. Results: LINC00968 expression reduced while hsa-miR-423-5p increased in BC tissues relative to adjacent normal tissues. Overexpression of LINC00968 was observed to inhibit BC cell proliferation, migration and tube formation abilities in vitro as well as tumor growth in vivo through inhibition of hsa-miR-423-5p. And hsa-miR-423-5p mediated BC cellular functions and tumor growth through down-regulating PROX1. LINC00968 was identified as a competing endogenous RNA to upregulate PROX1 by downregulating hsa-miR-423-5p. More importantly, it was found that LINC00968 increased PROX1 expression in vivo in a concentration-dependent manner. Conclusion: Taken together, this study suggests that LINC00968 inhibits the progression of BC through impeding hsa-miR-423-5p-mediated PROX1 inhibition. LINC00968 may be a potential therapeutic target for BC therapy that warrants further studies.

Keywords: LINC00968; MicroRNA-423-5p; angiogenesis; breast cancer; migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Animals
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Homeodomain Proteins / metabolism*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neovascularization, Pathologic / genetics*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Specific Pathogen-Free Organisms
  • Transfection
  • Tumor Suppressor Proteins / metabolism*
  • Up-Regulation / genetics*

Substances

  • Homeodomain Proteins
  • MIRN423 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein

Grant support

This study was supported by the Screening and Analysis of Specific microRNAs Expression in Peripheral Blood of Patients with Bone Metastasis after Breast Cancer Surgery and the Basic and Frontier Technology Research Projects from Science and Technology Department of Henan Province (No. 142300410271).