LncRNA HCP5 promotes triple negative breast cancer progression as a ceRNA to regulate BIRC3 by sponging miR-219a-5p

Cancer Med. 2019 Aug;8(9):4389-4403. doi: 10.1002/cam4.2335. Epub 2019 Jun 18.


Emerging evidence has suggested that long noncoding RNAs (lncRNA) involved in the development and progression of cancer. Triple negative breast cancer (TNBC) was an aggressive type of breast cancer with high rates of cancer recurrence and metastasis. The pathogenesis of TNBC is largely unknown. Recent studies suggested that lncRNA HCP5 plays an important role in carcinogenesis. The purpose of this study was to examine the function and mechanism of HCP5 in TNBC. We observed that HCP5 was upregulated in TNBC cell lines and specimens. HCP5 knockdown induced TNBC cell apoptosis, and inhibited cell proliferation and orthotopic xenograft tumor growth. RNA sequencing and antibody array suggested that HCP5 achieves its functions through regulating apoptosis pathway. Bioinformatics, luciferase and RIP experiments proved that both HCP5 and BIRC3 could competitively bind to miR-219a-5p. Increased BIRC3 and decreased miR-219a-5p were observed in TNBC tissues and cell lines. We then performed gain- and loss-of-function studies as well as rescue experiments in TNBC cells. The decrease of proliferation and migration due to HCP5 knockdown could be rescued when miR-219a-5p inhibitor or BIRC3 was transfected and vice versa. Our study suggested that lncRNA HCP5 promotes TNBC progression as a ceRNA to regulate BIRC3 by sponging miR-219a-5p. In a word, we revealed a new signaling pathway to mediate TNBC, and provided HCP5 as a new target for improving treatment of TNBC.

Keywords: BIRC3; HCP5; MiR-219a-5p; competing endogenous RNA; triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviral IAP Repeat-Containing 3 Protein / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • RNA, Long Noncoding / genetics*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology*
  • Up-Regulation*


  • HCP5 long noncoding RNA, human
  • MIRN219 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • BIRC3 protein, human
  • Baculoviral IAP Repeat-Containing 3 Protein