Analysis of carcinogenic signaling networks in endometrial cancer identifies RAB17 as a potential target

Zhou, Xing; Xia, Geqing; Liu, Yan; Xin, Xiaoyan; Shi, Rui; An, Lanfen; Zhang, Jun; Zhao, Rong; Zhao, Yingchao; Wang, Hongbo

doi:10.1002/jcp.29845

Cited by 5 publications

(5 citation statements)

References 27 publications

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“…34 , 35 In the latest report, RAB17 was highly expressed in endometrial cancer, which regulated the cell cycle and promoted the proliferation of endometrial cancer by promoting the phosphorylation of AKT and mTOR. 36 In our study, we observed a significantly higher expression of RAB17 in paclitaxel-resistant ovarian cancer cells A2780/PTX and SKOV3/PTX in comparison with paclitaxel-sensitive ovarian cancer cells A2780 and SKOV3 for the first time. We conducted a systematic investigation.…”

Section: Discussionsupporting

confidence: 57%

Knockdown of Circular RNA Hsa_circ_0000714 Can Regulate RAB17 by Sponging miR-370-3p to Reduce Paclitaxel Resistance of Ovarian Cancer Through CDK6/RB Pathway

Guo¹,

Li²,

Xi³

et al. 2020

OTT

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Purpose Paclitaxel resistance in ovarian cancer has become an urgent clinical problem. This study investigated the regulatory effects of RAB17 on the non-coding RNA network of the paclitaxel-resistant ovarian cancer cell A2780/PTX. Methods Microarray analysis was used to identify differentially expressed genes in paclitaxel-resistant cell A2780/PTX compared to the parent paclitaxel-sensitive cell A2780. Quantitative real-time PCR and Western blot were used to measure the expression of related mRNAs and proteins. The CCK8 assay was used to determine cell survival ratios and drug resistance indices in ovarian cancer cells. The clone forming assay was used to analyze the cell clone proliferation. Flow cytometry was used to analyze the cell cycle. Dual-luciferase reporter gene assays evaluated the relationship between the genes. Results RAB17 is highly expressed in A2780/PTX cells. RAB17 knockdown increased the cell sensitivity to paclitaxel, inhibited proliferation, and caused cell cycle arrest in the G1 phase in A2780/PTX. Western blot confirmed that RAB17 influenced cell behavior by activating the CDK6/RB signaling pathway. Bioinformatics analyses identified RAB17 as a new target by the microRNA miR-370-3p, and the latter was predicted to interact with circular RNA hsa_circ_0000714. Hsa_circ_0000714 indeed acted as a miRNA sponge for miR-370-3p allowing its regulation of RAB17 expression. This regulation was accomplished through the CDK6/RB signaling pathway. Conclusion Hsa_circ_0000714 acts as a sponge for miR-370-3p, and regulates RAB17 expression through the CDK6/RB signaling pathway, which plays a role in the malignant progression of the paclitaxel-resistant ovarian cancer cell A2780/PTX.

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Section: Discussionsupporting

confidence: 57%

Knockdown of Circular RNA Hsa_circ_0000714 Can Regulate RAB17 by Sponging miR-370-3p to Reduce Paclitaxel Resistance of Ovarian Cancer Through CDK6/RB Pathway

Guo¹,

Li²,

Xi³

et al. 2020

OTT

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“…2A and 2B). Several well-known metastasis genes were included in the list of DEGs, including TCF7 (Zhao et al 2023 ), MAPK13 (Tan et al 2010 ), RAB17 (Zhou et al 2021 ), CXCL10 (Ka et al 2023 ; Lee et al 2022 ; Shang et al 2022 ), CTSK (Khan et al 2021 ; Li et al 2019 ; Wu et al 2022 ), CCDC80 (Huang et al 2023 ), and ABCC2 (Sensorn et al 2016 ). In line with RNA-seq analysis, our qRT-PCR confirmed the elevated expression of the aforementioned DEGs ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection

Hao,

Dong,

Bai

et al. 2024

swwlxb

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Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study, we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of in vivo screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improves our understanding of the metastasis mechanisms, but also provides potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.

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“…RAB17 is a small GTPase that belongs to the Rab family. The expression of RAB17 was initially reported to be specific to ECs [ 57 ], although it has recently been detected in melanocytes [ 58 ], hippocampal neurons [ 59 ] and macrophages [ 60 ], and cancer cells such as Hela [ 61 ], breast cancer [ 62 ], non-small cell lung cancer [ 19 ] and endometrial cancer cells [ 63 ]. RAB17 regulates basolateral to apical transcytosis and sustains polarized sorting [ 20 ], which is similar to polarization during tube formation, where ECs are polarized towards the basement membrane matrix [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA-seq and bulk-seq identify RAB17 as a potential regulator of angiogenesis by human dermal microvascular endothelial cells in diabetic foot ulcers

Du,

Li,

et al. 2023

Burns &Amp; Trauma

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Background Angiogenesis is crucial in diabetic wound healing and is often impaired in diabetic foot ulcers (DFUs). Human dermal microvascular endothelial cells (HDMECs) are vital components in dermal angiogenesis; however, their functional and transcriptomic characteristics in DFU patients are not well understood. This study aimed to comprehensively analyse HDMECs from DFU patients and healthy controls and find the potential regulator of angiogenesis in DFUs. Methods HDMECs were isolated from skin specimens of DFU patients and healthy controls via magnetic-activated cell sorting. The proliferation, migration and tube-formation abilities of the cells were then compared between the experimental groups. Both bulk RNA sequencing (bulk-seq) and single-cell RNA-seq (scRNA-seq) were used to identify RAB17 as a potential marker of angiogenesis, which was further confirmed via weighted gene co-expression network analysis (WGCNA) and least absolute shrink and selection operator (LASSO) regression. The role of RAB17 in angiogenesis was examined through in vitro and in vivo experiments. Results The isolated HDMECs displayed typical markers of endothelial cells. HDMECs isolated from DFU patients showed considerably impaired tube formation, rather than proliferation or migration, compared to those from healthy controls. Gene set enrichment analysis (GSEA), fGSEA, and gene set variation analysis (GSVA) of bulk-seq and scRNA-seq indicated that angiogenesis was downregulated in DFU-HDMECs. LASSO regression identified two genes, RAB17 and CD200, as characteristic of DFU-HDMECs; additionally, the expression of RAB17 was found to be significantly reduced in DFU-HDMECs compared to that in the HDMECs of healthy controls. Overexpression of RAB17 was found to enhance angiogenesis, the expression of hypoxia inducible factor-1α and vascular endothelial growth factor A, and diabetic wound healing, partially through the mitogen-activated protein kinase/extracellular signal-regulated kinase signalling pathway. Conclusions Our findings suggest that the impaired angiogenic capacity in DFUs may be related to the dysregulated expression of RAB17 in HDMECs. The identification of RAB17 as a potential molecular target provides a potential avenue for the treatment of impaired angiogenesis in DFUs.

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Analysis of carcinogenic signaling networks in endometrial cancer identifies RAB17 as a potential target

Cited by 5 publications

References 27 publications

Knockdown of Circular RNA Hsa_circ_0000714 Can Regulate RAB17 by Sponging miR-370-3p to Reduce Paclitaxel Resistance of Ovarian Cancer Through CDK6/RB Pathway

Knockdown of Circular RNA Hsa_circ_0000714 Can Regulate RAB17 by Sponging miR-370-3p to Reduce Paclitaxel Resistance of Ovarian Cancer Through CDK6/RB Pathway

Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection

Single-cell RNA-seq and bulk-seq identify RAB17 as a potential regulator of angiogenesis by human dermal microvascular endothelial cells in diabetic foot ulcers

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