Rce1 expression in renal cell carcinoma and its regulatory effect on 786-O cell apoptosis through endoplasmic reticulum stress

Li, Jianjun; Wang, Delin; Liu, Junnan; Qin, Yunlang; Huang, Liangliang; Zeng, Qiangfeng; Xiao, Maolin; Hu, Jie; Yang, Qixin; Jiang, He; Li, Mai; Liu, Ying; Liu, Wujiang

doi:10.1093/abbs/gmx002

Cited by 6 publications

(6 citation statements)

References 29 publications

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“…Several studies related to ccRCC reported that ER stress contributes to the alleviation of cancer malignant phenotypes. Downregulation of Rce1 enables RCC cell apoptosis by driving the PERK signaling pathway ( Li et al, 2017 ). The silencing of the expression of MSRB3 enhanced the expression of ER stress-related genes and inhibited the proliferation, migration, and invasion of ccRCC cells ( Ye et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma

et al. 2022

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Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. The maximum number of deaths associated with kidney cancer can be attributed to ccRCC. Disruption of cellular proteostasis results in endoplasmic reticulum (ER) stress, which is associated with various aspects of cancer. It is noteworthy that the role of ER stress in the progression of ccRCC remains unclear. We classified 526 ccRCC samples identified from the TCGA database into the C1 and C2 subtypes by consensus clustering of the 295 ER stress-related genes. The ccRCC samples belonging to subtype C2 were in their advanced tumor stage and grade. These samples were characterized by poor prognosis and malignancy immune microenvironment. The upregulation of the inhibitory immune checkpoint gene expression and unique drug sensitivity were also observed. The differentially expressed genes between the two clusters were explored. An 11-gene ER stress-related prognostic risk model was constructed following the LASSO regression and Cox regression analyses. In addition, a nomogram was constructed by integrating the clinical parameters and risk scores. The calibration curves, ROC curves, and DCA curves helped validate the accuracy of the prediction when both the TCGA dataset and the external E-MTAB-1980 dataset were considered. Moreover, we analyzed the differentially expressed genes common to the E-MTAB-1980 and TCGA datasets to screen out new therapeutic compounds. In summary, our study can potentially help in the comprehensive understanding of ER stress in ccRCC and serve as a reference for future studies on novel prognostic biomarkers and treatments.

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Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma

et al. 2022

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“…Rce1 is a novel type II CAAX isoprenyl endopeptidase that can hydrolyze three amino acids from Ras to participate in posttranslational modifications that facilitates its relocalization to the plasma membrane (Hampton et al, ; Manolaridis et al, ). There is increasing evidence that Rce1 plays a crucial role in the development of multiple malignancies (Huang et al, ; Jaworski et al, ; J. Li et al, ). Based on a previous study of EMT in HCC, we collected 131 cases of HCC and matched paratumor tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Rce1 participates in posttranslational modification of Ras in the endoplasmic reticulum and undergoes subsequent methylation and additional transcription processing (Jaworski et al, ; Stout & Campbell, ). Research works have shown that Rce1 plays a crucial role in the cancerogenesis and development of various malignant tumors, such as renal cell carcinoma (J. Li et al, ), prostate cancer (Huang et al, ), and colorectal cancer (Shi et al, ). At present, Rce1 has not been studied in HCC and the specific molecular mechanism of Rce1 in the early invasion and metastasis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Research works have shown that Rce1 plays a crucial role in the cancerogenesis and development of various malignant tumors, such as renal cell carcinoma (J. Li et al, 2017), prostate cancer (Huang et al, 2016), and colorectal cancer (Shi et al, 2017). At present, Rce1 has not been studied in HCC and the specific molecular mechanism of Rce1 in the early invasion and metastasis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Rce1 suppresses invasion and metastasis of hepatocellular carcinoma via epithelial‐mesenchymal transition induced by the TGF‐β1/H‐Ras signaling pathway

Yang

et al. 2019

Journal Cellular Physiology

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Ras converting enzyme 1 (Rce1) plays an important role in invasion and metastasis of malignancy. However, the mechanism has not yet been fully explored in hepatocellular carcinoma (HCC). Primarily, we investigated the expression of Rce1 and H-Ras influence on patient prognosis through the clinical data. Further, we analyzed the regulatory effects of Rce1/H-Ras signal pathway on the epithelial-mesenchymal transition (EMT) in vitro and in vivo. Finally, we screened out the protein which bonds with Rce1 by CO-IP experiment to discuss the mechanism of Rce1 in EMT of HCC. This research revealed a significantly decreased expression of Rce1 in HCC compared with noncancerous tissues (p < .05). In contrast, H-Ras expression was increased in the tumor. The expression of them was a close association with the differentiation and tumor-node-metastasis (TNM) stage of the tumor (p < .001; p = .035, respectively) and Rce1 was an independent prognostic indicator (95%Cl: 0.193-0.821; p = .013). Through targeted regulation of Rce1 by cDNA or small interfering RNA, results show that the lower expression of Rce1 facilitated EMT and promoted the invasion and metastasis of HCC (p < .05). Furthermore, the CO-IP experiment unfolded that Rce1 could bond with farnesyltransferase-β (FNTB) which mediated the expression of H-Ras. Conclusions: Rce1 inhibits EMT via target regulation H-Ras and suppress the early invasion and metastasis of HCC. It may be a potential therapeutic target and prognostic indicator for HCC. K E Y W O R D S epithelial-mesenchymal transition, hepatocellular carcinoma, invasion and metastasis, ras converting enzyme 1, signaling pathway

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“…The development and testing of RPIs and MTIs substantially lag that of prenyl transferase inhibitors. Rce1 is also being investigated as a potential biomarker in various types of cancer, but its utility as a disease predictor remains far from being understood ( Huang et al 2016 ; Li et al 2017 ; Shi et al 2017 ).…”

Section: Clinical Relevance Of Rce1mentioning

confidence: 99%

Rce1: mechanism and inhibition

Hampton

Dore

Schmidt

2018

Critical Reviews in Biochemistry and Molecular Biology

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Ras converting enzyme 1 (Rce1) is an integral membrane endoprotease localized to the endoplasmic reticulum that mediates the cleavage of the carboxyl-terminal three amino acids from CaaX proteins, whose members play important roles in cell signaling processes. Examples include the Ras family of small GTPases, the γ-subunit of heterotrimeric GTPases, nuclear lamins, and protein kinases and phosphatases. CaaX proteins, especially Ras, have been implicated in cancer, and understanding the post-translational modifications of CaaX proteins would provide insight into their biological function and regulation. Many proteolytic mechanisms have been proposed for Rce1, but sequence alignment, mutational studies, topology, and recent crystallographic data point to a novel mechanism involving a glutamate-activated water and an oxyanion hole. Studies using in vivo and in vitro reporters of Rce1 activity have revealed that the enzyme cleaves only prenylated substrates and the identity of the a2 amino residue in the Ca1a2X sequence is most critical for recognition, preferring Ile, Leu, or Val. Substrate mimetics can be somewhat effective inhibitors of Rce1 in vitro. Small-molecule inhibitor discovery is currently limited by the lack of structural information on a eukaryotic enzyme, but a set of 8-hydroxyquinoline derivatives has demonstrated an ability to mislocalize all three mammalian Ras isoforms, giving optimism that potent, selective inhibitors might be developed. Much remains to be discovered regarding cleavage specificity, the impact of chemical inhibition, and the potential of Rce1 as a therapeutic target, not only for cancer, but also for other diseases.

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Rce1 expression in renal cell carcinoma and its regulatory effect on 786-O cell apoptosis through endoplasmic reticulum stress

Cited by 6 publications

References 29 publications

Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma

Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma

Rce1 suppresses invasion and metastasis of hepatocellular carcinoma via epithelial‐mesenchymal transition induced by the TGF‐β1/H‐Ras signaling pathway

Rce1: mechanism and inhibition

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