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. 2019 Nov 8:19:283.
doi: 10.1186/s12935-019-0998-4. eCollection 2019.

TRIM27 promotes the development of esophagus cancer via regulating PTEN/AKT signaling pathway

Liang Ma  1   2 , Ninghua Yao  3 , Ping Chen  2 , Zhixiang Zhuang  1
Affiliations

TRIM27 promotes the development of esophagus cancer via regulating PTEN/AKT signaling pathway

Liang Ma et al. Cancer Cell Int. .

Abstract

Background: Tripartite motif‑containing 27 (TRIM27) belongs to the TRIM protein family, which is closely related to the progression of some certain human cancers. Nevertheless, the biological function of TRIM27 in esophageal squamous cell carcinoma (ESCC) is still not clear. The aim of present research is to examine the function of TRIM27 in ESCC cells.

Methods: In the present study, RNA interference (RNAi) and lentiviral vector were used to knockdown and overexpression of TRIM27 in ESCC cells respectively. qRT-PCR and western blot were used to examine the expression of TRIM27 in ESCC cells. Cell counting kit-8 (CCK-8) assay was performed to determine the proliferation of cells.

Results: Our analyses indicated that TRIM27 was a pro-proliferation factor in ESCC cells. Moreover, overexpression of TRIM27 deeply suppressed the apoptosis of ESCC cells and accelerated its glucose uptake. In addition, an AKT inhibitor LY294002 was used to determine the connection between TRIM27 and AKT in ESCC cells. Our results demonstrated that TRIM27 has involved in the PI3/AKT signaling pathway. Moreover, TRIM27 interacted with PTEN and mediated its poly-ubiquitination in ESCC cells. Importantly, the glycolysis inhibitor 3-BrPA also inhibited the effect of TRIM27 on ESCC cells. Hence, TRIM27 also participated in the regulation of energy metabolism in ESCC cells.

Conclusions: This research not only gained a deep insight into the biological function of TRIM27 but also elucidated its potential target and signaling pathway in human ESCC cells.

Keywords: Esophagus cancer; PI3/AKT; PTEN; TRIM27.

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Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
TRIM27 was upregulated in ESCC tissues and cells. N normal, T tumor. a The relative mRNA level of TRIM27 detected in ESCC tissues (n = 25) and adjacent noncancerous samples (n = 18), ***p < 0.001 vs normal. b The protein content of TRIM27 examined in six pairs of ESCC tissues and matched adjacent samples, ***p < 0.001 vs normal. c, d Stands for the mRNA and protein level of TRIM27 in HECC, TE-1, TE-11, EAC-109 and KYSE150 cells respectively, ***p < 0.001 vs HECC
Fig. 2
Fig. 2
Knockdown and overexpression of TRIM27 in ESCC cells. a, b The mRNA and protein level of TRIM27 was deeply suppressed by siTRIM27 in KYSE150 and TE-11 cells, ***p < 0.001 vs siNC. c, d The TRIM27 was significantly upregulated by oeTRIM27 in TE-1 cells. ***p < 0.001 vs oeNC
Fig. 3
Fig. 3
Knockdown of TRIM27 inhibited the growth of ESCC cells. a, b The cell proliferation rate detected at 12 h, 24 h and 48 h after transfection with siNC, siTRIM27-1 and siTRIM27-2 in KYSE150 and TE-11 cells respectively, *p < 0.05 vs siNC, ***p < 0.001 vs siNC. c Cell apoptosis profile was upregulated in siTRIM27 transfected cells as indicated, ***p < 0.001 vs siNC. d The level of 2-NBDG was suppressed in siTRIM27 transfected cells, ***p < 0.001 vs siNC. e, f The protein level of GLUT1, HKII, cleaved caspase-3, AKT and p-AKT examined in different cells as indicated, ***p < 0.001 vs siNC
Fig. 4
Fig. 4
The inhibitor LY294002 and 3-BrPA inhibited the effect of TRIM27 in ESCC cells. a The cell proliferation rate detected at 12 h, 24 h and 48 h examined in different cells as indicated. *p < 0.05 vs oeNC, ***p < 0.001 vs oeNC. b Cell apoptosis profile was suppressed in oeTRIM27 transfected cells. **p < 0.01 vs oeNC, ***p < 0.001 vs oeNC; ###p < 0.001 vs oeTRIM27. c The level of 2-NBDG was upregulated in oeTRIM27 transfected cells. *p < 0.05 vs oeNC, ***p < 0.001 vs oeNC; ###p < 0.001 vs oeTRIM27. d The protein level of GLUT1, HKII, cleaved caspase-3, AKT and p-AKT examined in different cells as indicated, ***p < 0.001 vs oeNC; ###p < 0.001 vs oeTRIM27
Fig. 5
Fig. 5
TRIM27 interacted with PTEN and promoted its poly-ubiquitination in ESCC cells. a CoIP assay was performed to examine the interaction between TRIM27 and PTEN in ESCC cells. b siTRIM27 inhibited the poly-ubiquitination of PTEN in ESCC cells
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