The effect of lncRNA HOTAIR on chemoresistance of ovarian cancer through regulation of HOXA7

Biol Chem. 2018 Apr 25;399(5):485-497. doi: 10.1515/hsz-2017-0274.

Abstract

This study aimed at investigating the biological functions of long non-coding RNAs (lncRNAs) hox transcript antisense intergenic RNA (HOTAIR) in resistant ovarian cancer cells, exploring the regulation effect of HOTAIR on HOXA7, and investigating their influence on the chemosensitivity of ovarian cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for the verification of HOTAIR expression in resistant and sensitive groups. How HOTAIR downregulation affected cell proliferation, migration and invasion, and apoptosis were determined using the MTT assay and the colony formation assay, the Transwell assay and flow cytometry analysis, respectively. Immunohistochemistry was used to inspect the protein expression of HOXA7 in resistant and sensitive ovarian cancer tissues. The regulation relationship between HOTAIR and HOXA7 was investigated by qRT-PCR and Western blot. The effect of HOTAIR and HOXA7 on tumor growth was confirmed by the tumor xenograft model of nude mice. By knocking down HOXA7, HOTAIR downregulation restrained the ovarian cancer deterioration in functional experiments. Silencing of HOTAIR and HOXA7 could effectively inhibit tumor growth and increase chemosensitivity of ovarian tumors in nude mice. Downregulation of HOTAIR negatively affected the survival and activity of resistant ovarian cancer cells, and suppressed the expression of HOXA7. Silencing of HOTAIR and HOXA7 could increase the chemosensitivity of ovarian cancer cells, thus suppressing tumor development.

Keywords: Cisplatin; HOXA7; lncRNA HOTAIR; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation
  • Female
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • HOTAIR long untranslated RNA, human
  • HOXA7 protein, human
  • Homeodomain Proteins
  • RNA, Long Noncoding