Budding uninhibited by benzimidazoles 1 might be a poor prognosis biomarker promoting the progression of papillary thyroid cancer

被引:2
作者
Jiang, Wenjie [1 ]
Yu, Yan [2 ]
Bhandari, Adheesh [1 ,3 ]
Hirachan, Suzita [4 ]
Dong, Xubin [1 ,2 ]
Huang, Xiaoli [2 ]
Qu, Jinmiao [5 ]
Chen, Chengze [2 ,5 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 1, Dept Breast Surg, Wenzhou, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Affiliated Hosp 1, Dept Thyroid Surg, Wenzhou, Zhejiang, Peoples R China
[3] Primera Hosp, Dept Gen Surg, Breast & Thyroid Unit, Kathmandu, Nepal
[4] Tribhuvan Univ, Teaching Hosp, Dept Gen Surg, Breast & Thyroid Unit, Kathmandu, Nepal
[5] Wenzhou Med Univ, Affiliated Hosp 1, Dept Thyroid Surg, Wenzhou 325000, Zhejiang, Peoples R China
关键词
biomarker; BUB1; cancer; prognosis; PTC; thyroid; MITOTIC CHECKPOINT GENES; OVEREXPRESSION; ANEUPLOIDY; RECURRENCE; MECHANISMS; CARCINOMA; MUTATIONS; HBUB1; BUB1;
D O I
10.1002/tox.23812
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
BackgroundPapillary thyroid carcinoma (PTC) is one of the most widespread malignant tumors of the endocrine system, with a high incidence. Budding uninhibited by benzimidazoles 1 (BUB1), one of the spindle assembly checkpoint (SAC) genes, is a multitask protein kinase required for eukaryotic chromosome segregation. Although BUB1 has been explored in several types of cancer, its biological role and molecular mechanisms in PTC remain unclear. MethodsIn this study, we performed an examination of four public datasets along with local PTC cohorts and discovered that BUB1 was elevated in PTC compared to non-cancer tissues. High BUB1 expression was linked with the status of BRAF(V600E), RAS, and TERT after statistical analysis. ResultsClinically, BUB1 is associated with a variety of clinicopathological features in PTC patients. Interestingly, analysis of the TCGA database showed that BUB1 was closely associated with poor prognosis of PTC and significantly correlated with PFS. As determined by regression analysis, BUB1, and T stage were independent predictors of PTC and were related to BRAF(V600E) and lymph node metastatic status. By RT-qPCR, BUB1 was considerably overexpressed in PTC cell lines in comparison with normal thyroid epithelial cells. ConclusionWe confirmed that the knockdown of BUB1 in BCPAP and TPC1 cell lines significantly inhibited cell proliferation, cloning, and migration in vitro experiments. These results imply that BUB1 may be a significant oncogenic gene that is directly associated with the prognosis of PTC and may represent a future target for therapeutic intervention.
引用
收藏
页码:2047 / 2056
页数:10
相关论文
共 32 条
  • [1] Integrated Genomic Characterization of Papillary Thyroid Carcinoma
    Agrawal, Nishant
    Akbani, Rehan
    Aksoy, B. Arman
    Ally, Adrian
    Arachchi, Harindra
    Asa, Sylvia L.
    Auman, J. Todd
    Balasundaram, Miruna
    Balu, Saianand
    Baylin, Stephen B.
    Behera, Madhusmita
    Bernard, Brady
    Beroukhim, Rameen
    Bishop, Justin A.
    Black, Aaron D.
    Bodenheimer, Tom
    Boice, Lori
    Bootwalla, Moiz S.
    Bowen, Jay
    Bowlby, Reanne
    Bristow, Christopher A.
    Brookens, Robin
    Brooks, Denise
    Bryant, Robert
    Buda, Elizabeth
    Butterfield, Yaron S. N.
    Carling, Tobias
    Carlsen, Rebecca
    Carter, Scott L.
    Carty, Sally E.
    Chan, Timothy A.
    Chen, Amy Y.
    Cherniack, Andrew D.
    Cheung, Dorothy
    Chin, Lynda
    Cho, Juok
    Chu, Andy
    Chuah, Eric
    Cibulskis, Kristian
    Ciriello, Giovanni
    Clarke, Amanda
    Clayman, Gary L.
    Cope, Leslie
    Copland, John A.
    Covington, Kyle
    Danilova, Ludmila
    Davidsen, Tanja
    Demchok, John A.
    DiCara, Daniel
    Dhalla, Noreen
    [J]. CELL, 2014, 159 (03) : 676 - 690
  • [2] Mechanisms of aneuploidy in thyroid cancer cell lines and tissues:: evidence for mitotic checkpoint dysfunction without mutations in BUB1 and BUBR1
    Bin, OY
    Knauf, JA
    Ain, K
    Nacev, B
    Fagin, JA
    [J]. CLINICAL ENDOCRINOLOGY, 2002, 56 (03) : 341 - 350
  • [3] BUB1 and BUBR1: multifaceted kinases of the cell cycle
    Bolanos-Garcia, Victor M.
    Blundell, Tom L.
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 2011, 36 (03) : 141 - 150
  • [4] Mutations of mitotic checkpoint genes in human cancers
    Cahill, DP
    Lengauer, C
    Yu, J
    Riggins, GJ
    Willson, JKV
    Markowitz, SD
    Kinzler, KW
    Vogelstein, B
    [J]. NATURE, 1998, 392 (6673) : 300 - 303
  • [5] Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden
    Chalmers, Zachary R.
    Connelly, Caitlin F.
    Fabrizio, David
    Gay, Laurie
    Ali, Siraj M.
    Ennis, Riley
    Schrock, Alexa
    Campbell, Brittany
    Shlien, Adam
    Chmielecki, Juliann
    Huang, Franklin
    He, Yuting
    Sun, James
    Tabori, Uri
    Kennedy, Mark
    Lieber, Daniel S.
    Roels, Steven
    White, Jared
    Otto, Geoffrey A.
    Ross, Jeffrey S.
    Garraway, Levi
    Miller, Vincent A.
    Stephens, Phillip J.
    Frampton, Garrett M.
    [J]. GENOME MEDICINE, 2017, 9
  • [6] Recurrence-associated genes in papillary thyroid cancer: An analysis of data from The Cancer Genome Atlas
    Chien, Ming-Nan
    Yang, Po-Sheng
    Lee, Jie-Jen
    Wang, Tao-Yeuan
    Hsu, Yi-Chiung
    Cheng, Shih-Ping
    [J]. SURGERY, 2017, 161 (06) : 1642 - 1650
  • [7] Overexpression of BUB1B contributes to progression of prostate cancer and predicts poor outcome in patients with prostate cancer
    Fu, Xin
    Chen, Guo
    Cai, Zhi-duan
    Wang, Cong
    Liu, Ze-zhen
    Lin, Zhuo-yuan
    Wu, Yong-ding
    Liang, Yu-xiang
    Han, Zhao-dong
    Liu, Jun-chen
    Zhong, Wei-De
    [J]. ONCOTARGETS AND THERAPY, 2016, 9 : 2211 - 2220
  • [8] Glinsky GV, 2005, J CLIN INVEST, V115, P1503, DOI 10.1172/JCI23412
  • [9] Bub1 is required for maintaining cancer stem cells in breast cancer cell lines
    Han, Jeong Yoon
    Han, Yu Kyeong
    Park, Ga-Young
    Kim, Sung Dae
    Kim, Joong Sun
    Jo, Wol Soon
    Lee, Chang Geun
    [J]. SCIENTIFIC REPORTS, 2015, 5
  • [10] SACCHAROMYCES-CEREVISIAE GENES REQUIRED FOR CELL-CYCLE ARREST IN RESPONSE TO LOSS OF MICROTUBULE FUNCTION
    HOYT, MA
    TOTIS, L
    ROBERTS, BT
    [J]. CELL, 1991, 66 (03) : 507 - 517