Long Noncoding RNA FEZF1-AS1 Promotes Proliferation and Inhibits Apoptosis in Ovarian Cancer by Activation of JAK-STAT3 Pathway

Med Sci Monit. 2018 Nov 12:24:8088-8095. doi: 10.12659/MSM.911194.

Abstract

BACKGROUND Long noncoding RNAs (lncRNAs) have been acknowledged as important regulators in human cancers, including ovarian cancer. Several reports identified lncRNA FEZF1-AS1 as an oncogene in gastric cancer, colorectal carcinoma, and non-small cell lung cancer (NSCLC). However, the function of FEZF1-AS1 in ovarian cancer remains largely unknown. This study was aimed to investigate the role of FEZF1-AS1 in ovarian cancer. MATERIAL AND METHODS FEZF1-AS1 expression levels in pairs of ovarian cancer tissues and adjacent normal tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier curve analysis was used to determine the correlation between FEZF1-AS1 expression and prognosis in ovarian cancer patients. The effects of FEZF1-AS1 knockdown on ovarian cancer cell proliferation, cell-cycle, and apoptosis were analyzed by Cell Counting Kit-8 (CCK8) and Fluorescence activated Cell Sorting (FACS) assays. Western blot was utilized to assess the effect of FEZF1-AS1 on the activation of JAK-STAT3 pathway. RESULTS FEZF1-AS1 was overexpressed in ovarian cancer tissues compared to adjacent normal tissues. Consistently, FEZF1-AS1 expression was also upregulated in ovarian cancer cell lines compared with normal cell line. Furthermore, higher expression of FEZF1-AS1 in ovarian cancer patients contributed to poorer prognosis. FEZF1-AS1 knockdown significantly suppressed the proliferation and promoted apoptosis in ovarian cancer cells. In mechanism, FEZF1-AS1 regulated activation of JAK-STAT3 signaling pathway by modulating STAT3 phosphorylation. Knockdown of FEZF1-AS1 significantly impaired the phosphorylation of STAT3. CONCLUSIONS Our study demonstrated that FEZF1-AS1 exerted an oncogenic role in ovarian cancer via modulating JAK-STAT3 pathway.

MeSH terms

  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Female
  • Humans
  • Janus Kinase 1 / metabolism
  • Kaplan-Meier Estimate
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Prognosis
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Repressor Proteins
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcriptome

Substances

  • FEZF1 protein, human
  • RNA, Antisense
  • RNA, Long Noncoding
  • Repressor Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Transcription Factors
  • Janus Kinase 1