Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 3, Pages 1698-1713Publisher
WILEY
DOI: 10.1111/jcmm.14065
Keywords
apoptosis; autophagy; rectal adenocarcinoma; signalling pathway; tumour necrosis factor-alpha-induced protein 8-like 2
Categories
Funding
- National Natural Science Foundation of China [81670088, 81802718, U1504817]
- Foundation of Science & Technology Department of Henan Province, China [162102410009, 172102410019, 182102310335]
- Natural Science Foundation of Education Department of Henan Province, China [15A310017]
- Science Foundation of Kaifeng City, China [1608004, 1703016]
- Science Foundation of Henan University, China [yqpy20170044]
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Tumour necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is a tumour suppressor in many types of cancer. However, the mechanism of action of TIPE2 on the growth of rectal adenocarcinoma is unknown. Our results showed that the expression levels of TIPE2 in human rectal adenocarcinoma tissues were higher than those in adjacent non-tumour tissues. Overexpression of TIPE2 reduced the proliferation, migration, and invasion of human rectal adenocarcinoma cells and down-regulation of TIPE2 showed reverse effects. TIPE2 overexpression increased apoptosis through down-regulating the expression levels of Wnt3a, phospho (p)-beta-Catenin, and p-glycogen synthase kinase-3 beta in rectal adenocarcinoma cells, however, TIPE2 knockdown exhibited reverse trends. TIPE2 overexpression decreased autophagy by reducing the expression levels of p-Smad2, p-Smad3, and transforming growth factor-beta (TGF-beta) in rectal adenocarcinoma cells, however, TIPE2 knockdown showed opposite effects. Furthermore, TIPE2 overexpression reduced the growth of xenografted human rectal adenocarcinoma, whereas TIPE2 knockdown promoted the growth of rectal adenocarcinoma tumours by modulating angiogenesis. In conclusion, TIPE2 could regulate the proliferation, migration, and invasion of human rectal adenocarcinoma cells through Wnt/beta-Catenin and TGF-beta/Smad2/3 signalling pathways. TIPE2 is a potential therapeutic target for the treatment of rectal adenocarcinoma.
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