TRIM14 promotes cell proliferation and inhibits apoptosis by suppressing PTEN in colorectal cancer

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. In the current study...

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Bibliographic Details
Published in:Cancer management and research 2019-01, Vol.11, p.5725-5735
Main Authors: Shen, Weidong, Jin, Zhonghai, Tong, Xiuping, Wang, Haiying, Zhuang, Lilei, Lu, Xiaofeng, Wu, Shenbao
Format: Article
Language:English
Subjects:
AKT
Apoptosis
Bone cancer
Cell adhesion & migration
Cell cycle
Cell growth
Colorectal cancer
Cyclin-dependent kinases
Diabetes
Gastroenterology
Kinases
Medical prognosis
Original Research
Proteins
PTEN
TRIM14
Tumors
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Summary: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. 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. 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 and tensin 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. The present data demonstrate that TRIM14 overexpression promotes CRC cell proliferation, suggesting TRIM14 as an attractive therapeutic target for CRC.
ISSN:1179-1322
1179-1322
DOI:10.2147/CMAR.S210782