FOXD1-AS1 promotes malignant behaviours of prostate cancer cells via the miR-3167/YWHAZ axis

Andrologia. 2022 Feb;54(1):e14263. doi: 10.1111/and.14263. Epub 2021 Oct 21.

Abstract

Herein, the effect of long noncoding RNA forkhead box D1 antisense RNA 1 (FOXD1-AS1) on malignant phenotypes of prostate cancer (PCa) cells was investigated. FOXD1-AS1 presented high expression in PCa cells according to the results of RT-qPCR. As shown by cell counting kit-8 assays, colony formation assays, wound-healing assays, Transwell assays and flow cytometry analyses, silenced FOXD1-AS1 suppressed PCa cell viability, proliferation, migration and invasion and enhanced cell apoptosis. Additionally, FOXD1-AS1 was primarily localised in cytoplasm of PCa cells. RNA immunoprecipitation assays and luciferase reporter assays revealed that FOXD1-AS1 interacted with miR-3167 in PCa cells. MiR-3167 functioned as an anti-oncogene in PCa and miR-3167 overexpression suppressed cell proliferation while promoted cell apoptosis. Moreover, the downstream target of miR-3167 is mRNA YWHAZ. FOXD1-AS1 elevated the expression of YWHAZ by binding with miR-3167. The suppressive effect of miR-3167 on YWHAZ expression was reversed by FOXD1-AS1 overexpression. Furthermore, overexpressed YWHAZ reversed the suppressive effect of FOXD1-AS1 deficiency on malignant behaviours of PCa cells. Overall, FOXD1-AS1 facilitates malignant phenotypes of PCa cells by up-regulating YWHAZ via miR-3167. The study first reveals the molecular mechanism of FOXD1-AS1 in PCa, suggesting that FOXD1-AS1 and its downstream molecules might be prognostic biomarkers before medical treatment.

Keywords: FOXD1-AS1; YWHAZ; ceRNA; miR-3167; prostate cancer.

MeSH terms

  • 14-3-3 Proteins
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs* / genetics
  • Prostatic Neoplasms* / genetics
  • RNA, Antisense
  • RNA, Long Noncoding* / genetics

Substances

  • 14-3-3 Proteins
  • FOXD1 protein, human
  • Forkhead Transcription Factors
  • MicroRNAs
  • RNA, Antisense
  • RNA, Long Noncoding
  • YWHAZ protein, human