China Oncology ›› 2017, Vol. 27 ›› Issue (11): 860-866.doi: 10.19401/j.cnki.1007-3639.2017.11.004

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BRD4 induces proliferation, invasion and migration of thyroid cancer cells via SHH signaling pathway

JI Kailun1, LIU Qi2, MU Zuofeng2, MA Xiaodong2, LI Guolou2   

  1. 1. Clinical College of Weifang Medical University, Weifang 261053, Shandong Province, China; 2. Department of Breast and Thyroid Surgery, the Traditional Chinese Medicine Hospital of Weifang, Weifang 261041, Shandong Province, China
  • Online:2017-11-30 Published:2017-12-12
  • Contact: LI Guolou E-mail: guolouli@sina.com

Abstract: Background and purpose: Thyroid cancer is the endocrine malignant tumor with the highest incidence. Although comprehensive treatment has gotten considerable effect, some patients have low iodine uptake and poor 131I therapeutic effect in the subsequent treatment which causes recurrence and distant metastasis. Recent studies have found that double bromodomain-containing protein 4 (BRD4) plays a key role in promoting the progression of some malignant tumors. Therefore, we aimed to investigate the effect of BRD4 in papillary thyroid cancer (PTC), and search for the specific target of thyroid cancer. Methods: Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to examine the BRD4 expression in PTC tissue and para-cancerous tissue. PTC cell line TPC-1 was transfected with the siBRD4. And then the silence efficiency was examined by Western blot. The effects of BRD4 on cell viability, proliferation, migration and invasion were examined by MTT assay, colony formation assay and transwell assay. Besides, Western blot and RTFQ-PCR were used to examine the expression of sodium iodide symporter (NIS) and the downstream gene SHH and GLI1 of SHH signaling pathway. Results: BRD4 was overexpressed in PTC tissue (P<0.05). In vitro experiment showed that the viability, proliferation, invasion and migration of BRD4-silencing cells were decreased. Besides, the mRNA and protein expression levels of NIS were up-regulated while the downstream gene of SHH signaling pathway SHH and GLI1 were down-regulated (P<0.05). Conclusion: BRD4 would promote the invasion and migration of papillary thyroid cancer cells via up-regulating the genes of SHH signaling pathway. Silencing BRD4 can promote the expression of NIS. BRD4 may be a new target for the treatment of thyroid cancer.

Key words: Thyroid cancer, Double bromodomain-containing protein 4, SHH signaling pathway, Sodium iodide symporter gene