KIF23 enhances cell proliferation in pancreatic ductal adenocarcinoma and is a potent therapeutic target

被引:34
作者
Gao, Chun-Tao [1 ]
Ren, Jin [2 ]
Yu, Jie [1 ,3 ]
Li, Sheng-Nan [1 ]
Guo, Xiao-Fan [1 ]
Zhou, Yi-Zhang [1 ]
机构
[1] Tianjin Med Univ Canc Inst & Hosp, Dept Pancreat Canc, Natl Clin Res Ctr Canc, Tianjin Key Lab Canc Prevent & Therapy,Tianjins C, Huan Hu Xi Rd, Tianjin 300060, Peoples R China
[2] Shanxi Acad Med Sci, Shanxi Bethune Hosp, Taiyuan, Peoples R China
[3] Shanxi Med Univ, First Hosp, Taiyuan, Peoples R China
基金
中国国家自然科学基金;
关键词
Kinesin family member 23 (KIF23); proliferation; pancreatic cancer; prognosis; therapeutic target; KINESIN-LIKE PROTEIN; CANCER STATISTICS; EXPRESSION; CARCINOMA; SPINDLE; MKLP1; OVEREXPRESSION; MICROTUBULES; CHEMOTHERAPY; RADIOTHERAPY;
D O I
10.21037/atm-20-1970
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: In recent research, high expression of kinesin family member 23 (KIF23), one of the kinesin motor proteins involved in the regulation of cytokinesis, has been shown to be related to poor prognosis in glioma and paclitaxel-resistant gastric cancer, as a results of the enhancement of proliferation, migration, and invasion. In this study, we analyzed the role of KIF23 in the progression of pancreatic ductal adenocarcinoma. Methods: A bioinformatic method was used to analyze the KIF23 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the connection between high KIF23 expression and prognosis. We examined the expression of KIF23 using immunohistochemistry and analyzed the connection between the expression of KIF23 and clinicopathological features in pancreatic ductal adenocarcinoma patients. In addition, a colony formation assay, MTT assay, and western blot assay were performed in vitro, along with a mouse xenograft model in vivo, to analyze the effect of KIF23 on proliferation. Further, the correlation between KIF23 and CDCA8 was analyzed by TCGA and immunohistochemical data. Results: Bioinformatic results showed that KIF23 mRNA expression was higher in pancreatic tumor tissues than in normal pancreatic tissues and a poor prognosis has been linked to the high expression of KIF23. Immunohistochemistry revealed that KIF23 was highly expressed at the protein level and high expression of KIF23 correlated with adverse clinicopathological features. Our experimental results demonstrated that knockdown of KIF23 could inhibit the proliferation of pancreatic cells. Further, a positive correlation between KIF23 and CDCA8 expression existed, and KIF23 might promote pancreatic cancer proliferation by affecting CDCA8 expression. Conclusions: Our data showed that high expression of KIF23 is associated with a poor prognosis, and KIF23 might be a potential therapeutic target for pancreatic ductal adenocarcinoma.
引用
收藏
页数:15
相关论文
共 48 条
[1]  
[Anonymous], 2018, COCHRANE DATABASE SY
[2]  
[Anonymous], 2010, PATHOLOGE S2, DOI DOI 10.1007/S00292-010-1298-X
[3]   CCNE1 copy-number gain and overexpression identify ovarian clear cell carcinoma with a poor prognosis [J].
Ayhan, Ayse ;
Kuhn, Elisabetta ;
Wu, Ren-Chin ;
Ogawa, Hiroshi ;
Bahadirli-Talbott, Ash ;
Mao, Tsui-Lien ;
Sugimura, Haruhiko ;
Shih, Ie-Ming ;
Wang, Tian-Li .
MODERN PATHOLOGY, 2017, 30 (02) :297-303
[4]   Pancreatic Cancer: "A Riddle Wrapped in a Mystery inside an Enigma" [J].
Borazanci, Erkut ;
Dang, Chi V. ;
Robey, Robert W. ;
Bates, Susan E. ;
Chabot, John A. ;
Von Hoff, Daniel D. .
CLINICAL CANCER RESEARCH, 2017, 23 (07) :1629-1637
[5]   Microtubule targeting agents: from biophysics to proteomics [J].
Calligaris, D. ;
Verdier-Pinard, P. ;
Devred, F. ;
Villard, C. ;
Braguer, D. ;
Lafitte, Daniel .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2010, 67 (07) :1089-1104
[6]   Toward personalized TGFβ inhibition for pancreatic cancer [J].
Carr, Ryan M. ;
Fernandez-Zapico, Martin E. .
EMBO MOLECULAR MEDICINE, 2019, 11 (11)
[7]   Neoadjuvant Chemoradiation and Duration of Chemotherapy Before Surgical Resection for Pancreatic Cancer: Does Time Interval Between Radiotherapy and Surgery Matter? [J].
Chen, Kathryn T. ;
Devarajan, Karthik ;
Milestone, Barton N. ;
Cooper, Harry S. ;
Denlinger, Crystal ;
Cohen, Steven J. ;
Meyer, Joshua E. ;
Hoffman, John P. .
ANNALS OF SURGICAL ONCOLOGY, 2014, 21 (02) :662-669
[8]   Zebrafish mitotic kinesin-like protein 1 (Mklp1) functions in embryonic cytokinesis [J].
Chen, MC ;
Zhou, Y ;
Detrich, HW .
PHYSIOLOGICAL GENOMICS, 2002, 8 (01) :51-66
[9]   National cancer incidence and mortality in China, 2012 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Zuo, Tingting ;
Zeng, Hongmei ;
Zhang, Siwei ;
He, Jie .
CHINESE JOURNAL OF CANCER RESEARCH, 2016, 28 (01) :1-11
[10]   The molecular requirements for cytokinesis [J].
Glotzer, M .
SCIENCE, 2005, 307 (5716) :1735-1739