Downregulation of CSN6 attenuates papillary thyroid carcinoma progression by reducing Wnt/β-catenin signaling and sensitizes cancer cells to FH535 therapy

Duo Wen, Tian Liao, Ben Ma, Ning Qu, Rong Liang Shi, Zhong Wu Lu, Yu Long Wang, Wen Jun Wei, Qing Hai Ji

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The incidence of thyroid cancer has increased worldwide at a rate higher than that of any other cancer. CSN6 is overexpressed in many types of cancers, and such expression is linked to oncogenic activity. However, the detailed biological functions of CSN6 in papillary thyroid cancer (PTC) have not been well characterized. We investigated CSN6 expression in PTC specimens and cell lines. We used short-hairpin RNA-mediated gene silencing to explore the biological effects of CSN6 depletion in PTC cells. The combined effects of CSN6 silencing and FH535 therapy were assessed in terms of cell viability. The mechanism by which CSN6 regulated β-catenin expression was also analyzed. CSN6 levels were determined by real-time polymerase chain reaction (PCR) (mRNA), Western blotting, and immunochemistry (protein). The CCK-8 and migration assays and orthotopic xenograft transplantation were used to investigate the biological effects of CSN6. We assessed the combined effects of CSN6 silencing and FH535 on cell viability in vitro. We also analyzed the relationship between the CSN6 level and clinical pathological status. CSN6 was overexpressed in human PTCs, and loss of CSN6 attenuated tumor proliferation and migration both in vitro and in vivo. CSN6 stabilized β-catenin and facilitated the epidermal-to-mesenchymal transition (EMT) in PTC cells. CSN6 positively regulated β-catenin expression in a β-Trcp-dependent manner and triggered expression of several EMT-related genes regulated by β-catenin. CSN6 silencing sensitized PTC cells to FH535 therapy via downregulation of the Wnt/β–catenin signaling pathway. Finally, in PTC patients, the level of CSN6 was significantly (inversely) correlated with tumor size, the presence of multifocal lesions, and TNM stage. CSN6 overexpression in PTC is a strong indicator of enhanced tumor aggressiveness. CSN6 promotes PTC progression by inducing the EMT. CSN6 knockdown sensitizes PTC cells to FH535 therapy via downregulation of the Wnt/β–catenin signaling pathway.

Original languageEnglish (US)
Pages (from-to)285-296
Number of pages12
JournalCancer medicine
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

Catenins
Down-Regulation
Neoplasms
Wnt Signaling Pathway
Therapeutics
Cell Survival
Immunochemistry
Papillary Thyroid cancer
FH535
Sincalide
Heterologous Transplantation
Factor IX
Gene Silencing
Thyroid Neoplasms
Small Interfering RNA
Real-Time Polymerase Chain Reaction
Western Blotting
Cell Line
Messenger RNA

Keywords

  • CSN6
  • EMT
  • FH535
  • Wnt/β-catenin signaling pathway
  • papillary thyroid cancer
  • proliferation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Downregulation of CSN6 attenuates papillary thyroid carcinoma progression by reducing Wnt/β-catenin signaling and sensitizes cancer cells to FH535 therapy. / Wen, Duo; Liao, Tian; Ma, Ben; Qu, Ning; Shi, Rong Liang; Lu, Zhong Wu; Wang, Yu Long; Wei, Wen Jun; Ji, Qing Hai.

In: Cancer medicine, Vol. 7, No. 2, 01.02.2018, p. 285-296.

Research output: Contribution to journalArticle

Wen, Duo ; Liao, Tian ; Ma, Ben ; Qu, Ning ; Shi, Rong Liang ; Lu, Zhong Wu ; Wang, Yu Long ; Wei, Wen Jun ; Ji, Qing Hai. / Downregulation of CSN6 attenuates papillary thyroid carcinoma progression by reducing Wnt/β-catenin signaling and sensitizes cancer cells to FH535 therapy. In: Cancer medicine. 2018 ; Vol. 7, No. 2. pp. 285-296.
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