HOXD-AS1 Exerts Oncogenic Functions and Promotes Chemoresistance in Cisplatin-Resistant Cervical Cancer Cells

Hum Gene Ther. 2018 Dec;29(12):1438-1448. doi: 10.1089/hum.2017.256. Epub 2018 Sep 5.

Abstract

Long noncoding RNAs (lncRNAs) are important regulators in various human diseases. The lncRNA HOXD-AS1 is a tumor promoter in ovarian cancer, glioma, and lung cancer, but the specific effects of HOXD-AS1 on cervical cancer (CC) chemoresistance remain unclear. Here, the level of HOXD-AS1 in nonmalignant and CC tissues as well as in CC cells and cisplatin-resistant CC cells was determined. qRT-PCR indicated that HOXD-AS1 was overexpressed in CC tissues and cisplatin-resistant CC cells. Loss-of-function assays showed that downregulation of HOXD-AS1 expression suppressed chemoresistance of cisplatin-resistant CC cells. HOXD-AS1 targeted miR-130a-3p, and in gain-of-function assays miR-130a-3p could reverse cisplatin resistance of CC cells. miR-130a-3p in turn targeted zinc finger E-box homeobox 1 (ZEB1). These results collectively show that HOXD-AS1 can act as a competing endogenous RNA to upregulate ZEB1 expression via miR-130a-3p. The effects of the HOXD-AS1-miR-130a-3p-ZEB1 axis on cisplatin resistance of cisplatin-resistant CC cells were supported by rescue assay results. In summary, HOXD-AS1 enhanced chemoresistance of cisplatin-resistant CC cells by modulating miR-130a-3p/ZEB1 axis expression.

Keywords: HOXD-AS1; ZEB1, cisplatin-resistant; cervical cancer; miR-130a-3p.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Base Pairing
  • Base Sequence
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Plasmids / chemistry
  • Plasmids / metabolism
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transfection
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • Antineoplastic Agents
  • MIRN130 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • long non-coding RNA HOXD-AS1, human
  • Cisplatin