A novel all-trans retinoic acid derivative regulates cell cycle and differentiation of myelodysplastic syndrome cells by USO1

Li, Shufang; Deng, Guangcun; Su, Jingwen; Wang, Ke; Li, Lanlan; Song, Sujing; Peng, Xiaoqing; Chen, Feihu

doi:10.1016/j.ejphar.2021.174199

Cited by 2 publications

(6 citation statements)

References 46 publications

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“…As these proteins are all involved in Golgi transport system, it suggests that Golgi transport has a lesser role in LUSC tumourigenesis. Our findings and previously reported studies suggest that USO1, although involved in tumourigenesis, is most likely due to involve regulation of Erk (10,14,15), and is associated with a superior overall survival in LUAD and gastric cancer. The exact reason for this remains to be elucidated and warrants further investigation.…”

Section: Discussionsupporting

confidence: 80%

“…A recent study in multiple myeloma has shown that cells deficient for USO1 have reduced proliferation and increased apoptosis via regulation of the Erk pathway (14). Support for this comes from an additional study in MDS which has shown similar results, in that USO1 plays an oncogenic role by inactivating Raf/ERK signalling (15).…”

Section: Discussionmentioning

confidence: 87%

“…Interestingly GOSR1 has been shown to influence the sensitivity of lung cancer cells to cisplatin ( 50 ), and as high mRNA expression of this gene is associated with better OS in LUAD ( Table S1 ), this may therefore reflect a cohort of patients which may respond better to cisplatin based chemotherapy regimens. In this regard, high expression of USO1 results in reduced sensitivity to an all-trans retinoic acid (ATRA) derivative in myelodysplastic syndrome cells, while loss of USO1 enhances sensitivity ( 15 ). Given the potential for ATRA to target the cancer stem cell niche in lung cancer, whilst resensitizing cells to cisplatin ( 51 ), drugs that could potentially target USO1 may have potential utility in such regimens.…”

Section: Discussionmentioning

confidence: 99%

“…USO1 has been shown to have higher levels of expression in these cancers and its role in tumourigenesis contributes to cell proliferation and evasion of apoptosis. Furthermore, multiple studies have identified USO1 exerts its oncogenic role by interfering with the Erk signalling pathway (13)(14)(15). Currently, to our knowledge there have been no studies regarding the expression of USO1 and its clinical implications in NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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USO1 expression is dysregulated in non-small cell lung cancer

Keogh¹,

Ryan²,

Nur³

et al. 2022

Transl Lung Cancer Res

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Background: USO1 vesicle transport factor (USO1) is a vesicular transport factor crucial for Endoplasmic reticulum to Golgi transport and is required for transcytotic fusion and subsequent binding of the vesicles to the target membrane. USO1 has been studied in multiple cancers revealing high levels of expression and exerting its oncogenic role by increasing cell proliferation and evasion of apoptosis. Furthermore, multiple studies have implicated dysregulation of the Erk signalling pathway in the involvement of USO1 in multiple cancers. Overall survival (OS) in non-small cell lung cancer (NSCLC) remains low despite recent advances in treatments which are mainly due to the late stage of diagnosis and a significant cohort of patients lacking an available targeted therapy. The aim of this study was to investigate USO1 expression in NSCLC.Methods: An in-house NSCLC tissue microarray (TMA) comprising (n=204 patients) was stained for USO1. Scoring intensity (H score) was used to interrogate for correlations between USO1 expression and established prognostic factors, and OS. Further evaluation of the expression of USO1 in NSCLC was done using multiple online datasets including Lung Cancer Explorer (LCE), UALCAN, GEPIA, KM plotter, TIMER2 and MuTarget.Results: USO1, when highly expressed in lung adenocarcinomas (LUADs) leads to a significantly increased OS (P=0.028). There was no significant correlation between age, smoking status, lymph node status, tumour subgroup and stage. USO1 was significantly higher in patients with tumour size <5 cm compared to those ≥5 cm (P=0.016). Overexpression in LUAD occurred at an early stage being significantly upregulated in Stage 1 and N0 tumours. USO1's first neighbours, also involved in ER-Golgi transport have altered expression in LUAD and significantly impact overall survival. Overexpression occurred independently of commonly mutated genes in NSCLC and had no correlation with changes in the TME.Conclusions: This study highlights the importance of USO1 and ER-Golgi vesicular transport system in LUAD. USO1 overexpression occurs as an early event in LUAD and independently of commonly mutated genes in NSCLC and therefore may represent an attractive diagnostic biomarker as well as a potential target for treatment.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

USO1 expression is dysregulated in non-small cell lung cancer

Keogh¹,

Ryan²,

Nur³

et al. 2022

Transl Lung Cancer Res

View full text Add to dashboard Cite

show abstract

“…USO1 is aberrantly activated in MDS in vivo and in vitro , and silencing of USO1 promotes myeloid differentiation and inhibits proliferation of MDS cells. USO1 exerts its oncogenic effects by inactivating Raf/ERK signaling ( Li et al, 2021 ). 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR) is a ATRA derivative, and ATPR can induce MDS remission in vitro by decreasing USO1 and modifying Raf/ERK signaling ( Li et al, 2021 ).…”

Section: Malignant Hematologic Diseasesmentioning

confidence: 99%

All-trans retinoic acid in hematologic disorders: not just acute promyelocytic leukemia

Chen,

Tong,

et al. 2024

Front. Pharmacol.

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All-trans retinoic acid (ATRA) plays a role in tissue development, neural function, reproduction, vision, cell growth and differentiation, tumor immunity, and apoptosis. ATRA can act by inducing autophagic signaling, angiogenesis, cell differentiation, apoptosis, and immune function. In the blood system ATRA was first used with great success in acute promyelocytic leukemia (APL), where ATRA differentiated leukemia cells into mature granulocytes. ATRA can play a role not only in APL, but may also play a role in other hematologic diseases such as immune thrombocytopenia (ITP), myelodysplastic syndromes (MDS), non-APL acute myeloid leukemia (AML), aplastic anemia (AA), multiple myeloma (MM), etc., especially by regulating mesenchymal stem cells and regulatory T cells for the treatment of ITP. ATRA can also increase the expression of CD38 expressed by tumor cells, thus improving the efficacy of daratumumab and CD38-CART. In this review, we focus on the mechanism of action of ATRA, its role in various hematologic diseases, drug combinations, and ongoing clinical trials.

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A novel all-trans retinoic acid derivative regulates cell cycle and differentiation of myelodysplastic syndrome cells by USO1

Cited by 2 publications

References 46 publications

USO1 expression is dysregulated in non-small cell lung cancer

USO1 expression is dysregulated in non-small cell lung cancer

All-trans retinoic acid in hematologic disorders: not just acute promyelocytic leukemia

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