Knockdown of long non-coding RNA LINC00176 suppresses ovarian cancer progression by BCL3-mediated down-regulation of ceruloplasmin

J Cell Mol Med. 2020 Jan;24(1):202-213. doi: 10.1111/jcmm.14701. Epub 2019 Oct 30.

Abstract

Ovarian cancer is a common malignancy among women with some clinically approved diagnostic coding gene biomarkers. However, long non-coding RNAs (lncRNAs) have been indicated to play an important role in controlling tumorigenesis of ovarian cancer. Hereby, the aim of the study was to uncover the function of lncRNA LINC00176 in the development and progression of ovarian cancer by regulating ceruloplasmin (CP). Bioinformatics prediction in combination with RT-qPCR analysis for the expression pattern of LINC00176 revealed that LINC00176 was highly expressed in ovarian cancer tissues as well as in ovarian cancer cell lines, respectively. LINC00176 was predominantly localized in the nucleus. Delivery of si-LINC00176, oe-LINC00176, si-BCL3 and si-CP plasmids was conducted to explore the effects of LINC00176 on ovarian cancer. Promoted proliferation, migration and invasion along with reduced apoptosis were observed in cells treated with oe-LINC00176, while si-BCL3 and si-CP were able to block the promoting effects. Investigations with regard to the correlation between LINC00176 and promoter region of CP turned out to be positive via B-cell CLL/lymphoma 3 (BCL3) by means of dual-luciferase reporter gene assay, ChIP and RIP assays. Furthermore, oncogenic properties of the LINC00176/BCL3/CP axis were also demonstrated by tumour formation in vivo generated upon injecting cells in nude mice. Our results demonstrate that restored LINC00176 initiates tumorigenesis in ovarian cancer by increasing CP expression via recruiting BCL3, the mechanism of which represented a potential and promising therapeutic target for the disease.

Keywords: B-cell CLL/lymphoma 3; LINC00176; ceruloplasmin; epithelial-mesenchymal transition; ovarian cancer.

MeSH terms

  • Animals
  • Apoptosis
  • B-Cell Lymphoma 3 Protein / genetics
  • B-Cell Lymphoma 3 Protein / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Ceruloplasmin / genetics
  • Ceruloplasmin / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Ceruloplasmin