<p>The Role and Mechanism of S1PR5 in Colon Cancer</p>
Authors: Fei Bai
Xianli Yin
Jinfeng Zhao
Huijun Zhou
Shaofeng Jiang
Wu Liu
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: IDO1; NF-κB; S1PR5; colon cancer.
Affiliations: Key Laboratory of Nanobiological Technology of National Health Commission of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China., Department of Gastroenterology and Urology, Hunan Cancer Hospital & the Affiliated Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, People's Republic of China., Department of Gastroduodeno Pancreatic Surgery, Hunan Cancer Hospital & the Affiliated Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, People's Republic of China.

Abstract:  Purpose: To investigate the role and mechanism of S1PR5 in colon cancer. Materials and methods: Lentiviral infection and drug screening helped to establish colon cancer cell lines with stable overexpression and knockdown of S1PR5. Effects of S1PR5 expression on cell growth, proliferation, migration, and invasion were analyzed using a subcutaneous xenograft model in nude mice. Western blot (WB) was used to detect the effects of S1PR5 expression on p-AKT, STAT3, NF-κB, and p-JNK. The distribution of p65 was evaluated in nuclear and cytoplasmic fractions using WB. CCK-8, Transwell migration, and Transwell invasion assays analyzed cell growth, proliferation, migration, and invasion. qRT-PCR analysis revealed that S1PR5 expression was associated with altered expression levels of NF-κB downstream target genes, such as IL-6, TNF-α, and indoleamine 2, 3-dioxygenase 1 (IDO1). Results: qRT-PCR and WB analysis showed that the S1PR5 level in colon cancer cell lines-SW480, SW620, HCT116, and LoVo-was significantly higher than in NCM460, a healthy colonic epithelial cell line. SW620 and SW480, with high and low expression of S1PR5, respectively, were selected as model cell lines. S1PR5 knockdown in SW620 caused the growth rate, proliferation, migration, invasion, and subcutaneous tumor formation rate to decrease in mice, whereas S1PR5 overexpression in SW480 caused all of these parameters to increase. WB analysis showed an increase in phospho-p65 and its nuclear translocation. S1PR5 knockdown caused a decrease in phospho-p65 levels and its nuclear import, thereby inhibiting its activity. In S1PR5 knockdown and overexpressing cells, p65 was overexpressed and knocked down, respectively. qRT-PCR and WB showed that S1PR5 over-expression up-regulates IDO1, and S1PR5 knockdown inhibits IDO1. CCK-8 and Transwell assays showed that p65 and IDO1 overexpression antagonizes the antitumor effect of S1PR5 knockdown, and that p65 and IDO1 knockdown antagonizes the tumorigenic effect of S1PR5 overexpression. Conclusion: S1PR5 overexpression promotes the growth, migration, and invasion of cancer by activating the NF-κB/IDO1 signaling pathway. 

Retracted: Yes

PubPeer comments:
 Figs 3, 5. Same actin band but horizontally flipped. ![file] ![file] , 
 *[right]* Figure 8 from [Liu et al (2019)] .  Effect of Xanthohumol on the Ras MEK ERK signalling pathway in HT-29 cells as depicted by Western blot analysis. It was found that the expression of Ras decreased concentration-dependently in the HT-29 cells. Moreover, the phosphorylation of MEK and ERK was also suppressed by Xanthohumol. *[left]* Figure 8 from [Xu et al (2020)] .  Western blot analysis showing the effect of Shionone on the MEK ERK and STAT3 signalling pathway in SK-BR-3 cells. The Figure shows that the expression of p-ERK, p-MEK and p-STAT-3 decreases in a dose-dependent manner upon Shionone treatment . ![file] , 
 The paper has undergone a stealth revision or correction, replacing the offending bands in Figs 4 and 8. In the absence of any explanation of how the figures originally came to contain bands overlapping with (respectively) Fig 5, and another paper by different authors, I imagine them as assemblages of modular elements. The version currently provided on the journal website was created modified on 29 January 2021. ![file] Interested readers can still consult the original version (created 7 December 2019) via a copy [archived at ResearchGate] . ,