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CDKL1 promotes tumor proliferation and invasion in colorectal cancer

Authors Qin C, Ren L, Ji M, Lv S, Wei Y, Zhu D, Lin Q, Xu P, Chang W, Xu J

Received 23 January 2017

Accepted for publication 23 February 2017

Published 16 March 2017 Volume 2017:10 Pages 1613—1624

DOI https://doi.org/10.2147/OTT.S133014

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai

Chunzhi Qin,1,* Li Ren,1,* Meiling Ji,1,* Shixu Lv,2,* Ye Wei,1 Dexiang Zhu,1 Qi Lin,1 Pingping Xu,1 Wenju Chang,1 Jianmin Xu1

1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 2Department of Surgical Oncology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China

*These authors contributed equally to this work

Background: CDKL1 is a member of the cell division cycle 2 (CDC2)-related serine threonine protein kinase family and is overexpressed in malignant tumors such as melanoma, breast cancer, and gastric cancer.
Objective: This study aimed to evaluate whether CDKL1 can serve as a potential molecular target for colorectal cancer therapy.
Materials and methods: Expression of CDKL1 in colorectal cancer tissues and cell lines was measured by immunohistochemistry and Western blot, respectively. To investigate the role of CDKL1 in colorectal cancer, CDKL1-small hairpin RNA-expressing lentivirus was constructed and infected into HCT116 and Caco2 cells. The effects of RNA interference (RNAi)-mediated CDKL1 downregulation on cell proliferation and invasion were assessed by CCK-8, colony formation, transwell, and tumorigenicity assays in nude mice. The effects of CDKL1 downregulation on cell cycle and apoptosis were analyzed by flow cytometry. Furthermore, microarray method and data analysis elucidated the molecular mechanisms underlying the phenomenon.
Results: CDKL1 protein was overexpressed in colorectal cancer tissues compared with paired normal tissues. Knockdown of CDKL1 in HCT116 and Caco2 significantly inhibited cell growth, colony formation ability, tumor invasion, and G1–S phase transition of the cell cycle. The knockdown of CDKL1 stimulated the upregulation of p15 and retinoblastoma protein.
Conclusion: CDKL1 plays a vital role in tumor proliferation and invasion in colorectal cancer in vitro and in vivo and, thus, may be considered as a valuable target for therapeutic intervention.

Keywords: CDKL1, cell cycle, protein kinases, colorectal cancer

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