KIF23 enhances cell proliferation in pancreatic ductal adenocarcinoma and is a potent therapeutic target
被引:34
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作者:
Gao, Chun-Tao
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机构:
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 ChinaTianjin 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
Gao, Chun-Tao
[1
]
Ren, Jin
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机构:
Shanxi Acad Med Sci, Shanxi Bethune Hosp, Taiyuan, Peoples R ChinaTianjin 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
Ren, Jin
[2
]
Yu, Jie
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机构:
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
Shanxi Med Univ, First Hosp, Taiyuan, Peoples R ChinaTianjin 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
Yu, Jie
[1
,3
]
Li, Sheng-Nan
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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 ChinaTianjin 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
Li, Sheng-Nan
[1
]
Guo, Xiao-Fan
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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 ChinaTianjin 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
Guo, Xiao-Fan
[1
]
Zhou, Yi-Zhang
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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 ChinaTianjin 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
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
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.
机构:
Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USAUniv Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Gautam, Shailendra K.
Kumar, Sushil
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Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USAUniv Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Kumar, Sushil
Cannon, Andrew
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Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USAUniv Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Cannon, Andrew
Hall, Bradley
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机构:
Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Univ Nebraska Med Ctr, Dept Surg, Omaha, NE USAUniv Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Hall, Bradley
Bhatia, Rakesh
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Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USAUniv Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Bhatia, Rakesh
Nasser, Mohd Wasim
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Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USAUniv Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Nasser, Mohd Wasim
Mahapatra, Sidharth
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机构:
Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Univ Nebraska Med Ctr, Dept Pediat, Omaha, NE USA
Univ Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USAUniv Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Mahapatra, Sidharth
Batra, Surinder K.
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机构:
Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE USA
Univ Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USAUniv Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Batra, Surinder K.
Jain, Maneesh
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机构:
Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
Univ Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USAUniv Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA
机构:
Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, ItalyFdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, Italy
Nichetti, Federico
Marra, Antonio
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机构:
Azienda Osped San Paolo, Med Oncol Unit, Milan, ItalyFdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, Italy
Marra, Antonio
Corti, Francesca
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机构:
Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, ItalyFdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, Italy
Corti, Francesca
Guidi, Alessandro
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机构:
Azienda Osped San Gerardo, Med Oncol Unit, Monza, ItalyFdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, Italy
Guidi, Alessandro
Raimondi, Alessandra
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Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, ItalyFdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, Italy
Raimondi, Alessandra
Prinzi, Natalie
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机构:
Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, ItalyFdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, Italy
Prinzi, Natalie
Braud, Filippo de
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h-index: 0
机构:
Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, Italy
Univ Milan, Dept Oncol, Milan, ItalyFdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, Italy
Braud, Filippo de
Pusceddu, Sara
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h-index: 0
机构:
Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, ItalyFdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Via Venezian 1, I-20133 Milan, Italy
机构:
Newcastle Univ, Biosciences Inst, Newcastle Fibrosis Res Grp, Newcastle Upon Tyne, Tyne & Wear, EnglandNewcastle Univ, Biosciences Inst, Newcastle Fibrosis Res Grp, Newcastle Upon Tyne, Tyne & Wear, England
Borrello, M. Teresa
Martin, Mickenzie B.
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h-index: 0
机构:
Univ Western Ontario, Schulich Sch Med & Dent, Depts Physiol & Pharmacol Paediat & Oncol, London, ON, Canada
Lawson Hlth Res Inst, Childrens Hlth Res Inst, London, ON, CanadaNewcastle Univ, Biosciences Inst, Newcastle Fibrosis Res Grp, Newcastle Upon Tyne, Tyne & Wear, England
Martin, Mickenzie B.
Pin, Christopher L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Western Ontario, Schulich Sch Med & Dent, Depts Physiol & Pharmacol Paediat & Oncol, London, ON, Canada
Lawson Hlth Res Inst, Childrens Hlth Res Inst, London, ON, CanadaNewcastle Univ, Biosciences Inst, Newcastle Fibrosis Res Grp, Newcastle Upon Tyne, Tyne & Wear, England