Expression of the lncRNA ZFAS1 in cervical cancer and its correlation with prognosis and chemosensitivity

Gene. 2019 May 15:696:105-112. doi: 10.1016/j.gene.2019.01.025. Epub 2019 Feb 7.

Abstract

Objective: To investigate the expression of the lncRNA ZFAS1 in cervical cancer and its relationship with patient prognosis and cervical cancer cell chemosensitivity.

Methods: The expression of ZFAS1 in cervical cancer tissues and cell lines was detected by qRT-PCR. The cervical cancer CaSki and the HeLa cell lines were transfected to be divided into Blank, siR-Control, and siR-ZFAS1 groups. MTT, wound-healing, and transwell assays were used to evaluate cell biological function. Cisplatin with different concentrations was used to treat cells in different transfection groups, and MTT assays were used to detect the cell growth inhibition rate and the half-inhibitory concentration (IC50) of cisplatin was measured. Cell apoptosis was determined by flow cytometry. A xenograft mouse model was used to investigate the effects of siR-ZFAS1 on the chemosensitivity to cisplatin.

Results: ZFAS1 was significantly upregulated in cervical cancer tissues and cell lines, and increased ZFAS1 levels led to poor prognoses in patients. In addition, cells in the siR-ZFAS1 group showed remarkably reduced ZFAS1 expression as well as cell proliferation, invasion and migration. After being treated with cisplatin at different concentrations, cells in the siR-ZFAS1 group had dramatically increased cell growth inhibition and apoptosis but lower cisplatin IC50s. In addition, siR-ZFAS1 reduced the volumes and weights of tumors in nude mice treated with cisplatin and enhanced the chemosensitivity of cervical cancer cells to cisplatin.

Conclusion: The lncRNA ZFAS1 was upregulated in cervical cancer tissues, and its high expression indicated a poor prognosis. Silencing ZFAS1 may inhibit cell proliferation, migration and invasion and enhance cisplatin chemosensitivity.

Keywords: Cervical cancer; Chemosensitivity; Cisplatin; LncRNA; Prognosis; ZFAS1.

MeSH terms

  • Adult
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cervix Uteri / pathology
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Survival Analysis
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • ZFAS1 long non-coding RNA, human
  • Cisplatin