TRIM14 promotes cell proliferation and inhibits apoptosis by suppressing PTEN in colorectal cancer
Authors Shen W, Jin Z, Tong X, Wang H, Zhuang L, Lu X, Wu S
Received 1 April 2019
Accepted for publication 23 May 2019
Published 24 June 2019 Volume 2019:11 Pages 5725—5735
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Dr Kenan Onel
Weidong Shen,1,* Zhonghai Jin,2,* Xiuping Tong,2 Haiying Wang,2 Lilei Zhuang,2 Xiaofeng Lu,2 Shenbao Wu2
1Department of Gastroenterology, Jiangyin Hospital Affiliated to Nantong University, Jiangyin, People’s Republic of China; 2Department of Gastroenterology, Yiwu Hospital, Wenzhou Medical University, Yiwu, People’s Republic of China
*These authors contributed equally to this work
Background: Colorectal cancer (CRC) is among the most frequent and lethal malignancies worldwide. Although great advances have been made in the treatment of CRC, prognosis remains poor. Our previous study indicated that tripartite motif-containing 14 (TRIM14) was upregulated in CRC samples.
Methods: In the current study, the association between TRIM14 and CRC was investigated. Protein expression was determined by Western blotting and immunohistochemistry. Further, the biological roles of TRIM14 in CRC cell proliferation and apoptosis were explored both in vitro and in vivo.
Results: We observed that increased TRIM14 expression in CRC tissues was closely related with aggressive clinicopathological characteristics and poor prognosis. TRIM14 knockdown markedly reduced proliferation and increased apoptosis in HT-29 and SW620 cells, whereas TRIM14 overexpression in LoVo cells displayed opposite results. Xenograft experiments using HT-29 cells confirmed suppression of tumor growth and induction of apoptosis upon TRIM14 knockdown in vivo. Furthermore, downregulation of TRIM14 inhibited the AKT pathway, as indicated by reduced levels of phosphorylated AKT, Bcl-2 and Cyclin D1, and elevated levels of phosphatase andtensin homology (PTEN) and p27. In addition, TRIM14 colocalized with PTEN in the cytoplasm and induced PTEN ubiquitination. Moreover, PTEN overexpression significantly inhibited pro-proliferative effects of TRIM14, indicating an involvement of PTEN/AKT signaling in mediating TRIM14 functions.
Conclusions: The present data demonstrate that TRIM14 overexpression promotes CRC cell proliferation, suggesting TRIM14 as an attractive therapeutic target for CRC.
Keywords: colorectal cancer, TRIM14, PTEN, AKT
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