OncoTargets and Therapy (Aug 2019)

BRMS1 downregulation is a poor prognostic biomarker in anaplastic thyroid carcinoma patients

  • Wu Y,
  • Wang H,
  • Zhi J,
  • Hu L,
  • Hou X,
  • Ruan X,
  • Zheng X,
  • Liu H,
  • Gao M

Journal volume & issue
Vol. Volume 12
pp. 6937 – 6945

Abstract

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Yu Wu,1–5,* Huijuan Wang,1–4,* Jingtai Zhi,1–4,* Linfei Hu,1–4 Xiukun Hou,1–4 Xianhui Ruan,1–4 Xiangqian Zheng,1–4 Hui Liu,5 Ming Gao1–41Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300600, People’s Republic of China; 2Department of National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300600, People’s Republic of China; 3Department of Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300600, People’s Republic of China; 4Department of Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300600, People’s Republic of China; 5Department of Head and Neck Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, People’s Republic of ChinaCorrespondence: Hui LiuDepartment of Head and Neck Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, People’s Republic of ChinaTel +86 1 380 506 9511Email [email protected] GaoDepartment of Thyroid and Neck Tumor, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People’s Republic of ChinaTel +86 1 382 088 1516Email [email protected]*These authors contributed equally to this workBackground: Anaplastic thyroid carcinoma (ATC) is the most aggressive cancer in humans with no optimal treatment strategy available. The molecular mechanisms of ATC remain unclear. The aim of this study was to investigate the prognostic value and role of BRMS1 in the progression of ATC.Methods: BRMS1 expression was examined in thyroid cell lines using Western blot analysis. Immunohistochemistry was also performed to assess BRMS1 expression in ATC and papillary thyroid cancer (PTC) tissue. Cell proliferation assays, colony formation analysis, cell migration assays, cell apoptosis analysis, and animal studies were used to examine the effects of BRMS1 expression on ATC progression.Results: The expression of BRMS1 was significantly lower in ATC than in PTC and was associated with poor prognosis in ATC patients. Downregulation of BRMS1 expression promoted the proliferation and migration of 8505C cells and decreased their expression of CX43. Over-expressed BRMS1 promoted the apoptosis and impaired the proliferation and migration of CAL-62 cells via upregulated CX43. In vivo, BRMS1 significantly promoted apoptosis and impaired cell proliferation.Conclusion: Taken together, these findings demonstrate that decreased expression of BRMS1 is a poor prognostic biomarker in ATC patients. BRMS1 significantly promoted apoptosis and impaired cell proliferation via CX43 and P53. Loss of BRMS1 expression is therefore, one of the key pathomechanisms in ATC.Keywords: BRMS1, anaplastic thyroid carcinoma, prognosis, CX43

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