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Article ; Online: LncRNA RGMB-AS1 inhibits HMOX1 ubiquitination and NAA10 activation to induce ferroptosis in non-small cell lung cancer.

Gao, Gui-Bin / Chen, Liang / Pan, Jia-Feng / Lei, Tao / Cai, Xin / Hao, Zhexue / Wang, Qi / Shan, Ge / Li, Jin

2024 Volume 590, Page(s) 216826

Abstract: Ferroptosis, an iron-dependent regulated cell death caused by excessive lipid peroxide accumulation, has emerged as a promising therapeutic target in various cancers, including non-small cell lung cancer (NSCLC). In this study, we identified the long non- ...

Abstract	Ferroptosis, an iron-dependent regulated cell death caused by excessive lipid peroxide accumulation, has emerged as a promising therapeutic target in various cancers, including non-small cell lung cancer (NSCLC). In this study, we identified the long non-coding RNA RGMB-AS1 as a key regulator of ferroptosis in NSCLC. Mechanistically, RGMB-AS1 interacted with heme oxygenase 1 (HMOX1) and prevented its ubiquitination by the E3 ligase TRC8, leading to increased HMOX1 stability and enhanced ferroptosis. Additionally, RGMB-AS1 bound to the 82-87 amino acid region of N-alpha-acetyltransferase 10 (NAA10), stimulating its acetyltransferase activity and promoting the conversion of acetyl-CoA to HMG-CoA, further contributing to ferroptosis. The RGMB-AS1-HMOX1 and RGMB-AS1-NAA10 axes synergistically inhibited NSCLC growth both in vitro and in vivo. Clinically, low RGMB-AS1 expression was associated with advanced tumor stage and poor overall survival in NSCLC patients. Furthermore, adeno-associated virus-mediated RGMB-AS1 overexpression significantly suppressed tumor growth in mouse xenograft models. Our findings uncover a novel lncRNA-mediated regulatory mechanism of ferroptosis and highlight the potential of RGMB-AS1 as a prognostic biomarker and therapeutic target in NSCLC.
MeSH term(s)	Ferroptosis/genetics ; Humans ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Lung Neoplasms/metabolism ; Animals ; Ubiquitination ; Heme Oxygenase-1/genetics ; Heme Oxygenase-1/metabolism ; Mice ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Mice, Nude ; A549 Cells ; Xenograft Model Antitumor Assays ; Cell Proliferation
Chemical Substances	RNA, Long Noncoding ; Heme Oxygenase-1 (EC 1.14.14.18) ; HMOX1 protein, human (EC 1.14.14.18)
Language	English
Publishing date	2024-04-02
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2024.216826
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Article: Evaluating the Rhizosphere and Endophytic Microbiomes of a Bamboo Plant in Response to the Long-Term Application of Heavy Organic Amendment

Zhang, Xiaoping / Huang, Zhiyuan / Zhong, Zheke / Li, Qiaoling / Bian, Fangyuan / Gao, Guibin / Yang, Chuanbao / Wen, Xing

Plants. 2022 Aug. 16, v. 11, no. 16

2022

Abstract: Root-associated bacteria play a major role in plant health and productivity. However, how organic amendment influences root-associated bacteria is uncertain in Lei bamboo (Phyllostachys praecox) plantations. Here, we compared the rhizosphere and ... ...

Abstract	Root-associated bacteria play a major role in plant health and productivity. However, how organic amendment influences root-associated bacteria is uncertain in Lei bamboo (Phyllostachys praecox) plantations. Here, we compared the rhizosphere and endophytic microbiomes in two Lei bamboo plantations with (IMS) and without (TMS) the application of organic amendment for 16 years. The results showed IMS significantly increased (p < 0.05) the relative abundance of Proteobacteria and significantly decreased (p < 0.05) the relative abundance of Acidobacteria, Bacteroidetes, and Verrucomicrobiota. The root endophytic Proteobacteria and Acidobacteria were significantly higher in abundance (p < 0.05) in the IMS than in the TMS, while Actinobacteria and Firmicutes were significantly lower in abundance. Five taxa were assigned to Proteobacteria and Acidobacteria, which were identified as keystones in the rhizosphere soil microbiome, while two species taxonomically affiliated with Proteobacteria were identified as keystones in the root endophytic microbiota, indicating this phylum can be an indicator for a root-associated microbiome in response to IMS. The soil pH, soil total organic carbon (TOC), total nitrogen (TN), total phosphorus (TP), available potassium (AK), and TOC:TP ratio were significantly correlated (p < 0.05) with the bacterial community composition of both rhizosphere soils and root endophytes. TMS increased the microbial network complexity of root endophytes but decreased the microbial network complexity of rhizosphere soil. Our results suggest IMS shapes the rhizosphere and endophytic bacterial community compositions and their interactions differently, which should be paid attention to when designing management practices for the sustainable development of forest ecosystems.
Keywords	Acidobacteria ; Actinobacteria ; Bacteroidetes ; Firmicutes ; Phyllostachys violascens ; Proteobacteria ; bacterial communities ; bamboos ; community structure ; endophytes ; forests ; microbiome ; plant health ; potassium ; rhizosphere ; soil microorganisms ; soil pH ; sustainable development ; total nitrogen ; total organic carbon ; total phosphorus
Language	English
Dates of publication	2022-0816
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704341-1
ISSN	2223-7747
ISSN	2223-7747
DOI	10.3390/plants11162129
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Post-translational modifications of CDK5 and their biological roles in cancer.

Gao, Gui-Bin / Sun, Yue / Fang, Run-Dong / Wang, Ying / Wang, Yang / He, Qing-Yu

Molecular biomedicine

2021 Volume 2, Issue 1, Page(s) 22

Abstract: Post-translational modifications (PTMs) of Cyclin-dependent kinase 5 (CDK5) have emerged as important regulatory mechanisms that modulate cancer development in patients. Though CDK5 is an atypical member of the cyclin-dependent kinase family, its ... ...

Abstract	Post-translational modifications (PTMs) of Cyclin-dependent kinase 5 (CDK5) have emerged as important regulatory mechanisms that modulate cancer development in patients. Though CDK5 is an atypical member of the cyclin-dependent kinase family, its aberrant expression links to cell proliferation, DNA damage response, apoptosis, migration and angiogenesis in cancer. Current studies suggested that, new PTMs on CDK5, including S-nitrosylation, sumoylation, and acetylation, serve as molecular switches to control the kinase activity of CDK5 in the cell. However, a majority of these modifications and their biological significance in cancer remain uncharacterized. In this review, we discussed the role of PTMs on CDK5-mediated signaling cascade, and their possible mechanisms of action in malignant tumors, as well as the challenges and future perspectives in this field. On the basis of the newly identified regulatory signaling pathways of CDK5 related to PTMs, researchers have investigated the cancer therapeutic potential of chemical compounds, small-molecule inhibitors, and competitive peptides by targeting CDK5 and its PTMs. Results of these preclinical studies demonstrated that targeting PTMs of CDK5 yields promising antitumor effects and that clinical translation of these therapeutic strategies is warranted.
Language	English
Publishing date	2021-07-20
Publishing country	Singapore
Document type	Journal Article ; Review
ISSN	2662-8651
ISSN (online)	2662-8651
DOI	10.1186/s43556-021-00029-0
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Article: Evaluating the Rhizosphere and Endophytic Microbiomes of a Bamboo Plant in Response to the Long-Term Application of Heavy Organic Amendment.

Zhang, Xiaoping / Huang, Zhiyuan / Zhong, Zheke / Li, Qiaoling / Bian, Fangyuan / Gao, Guibin / Yang, Chuanbao / Wen, Xing

Plants (Basel, Switzerland)

2022 Volume 11, Issue 16

Abstract	Root-associated bacteria play a major role in plant health and productivity. However, how organic amendment influences root-associated bacteria is uncertain in Lei bamboo (Phyllostachys praecox) plantations. Here, we compared the rhizosphere and endophytic microbiomes in two Lei bamboo plantations with (IMS) and without (TMS) the application of organic amendment for 16 years. The results showed IMS significantly increased (p < 0.05) the relative abundance of Proteobacteria and significantly decreased (p < 0.05) the relative abundance of Acidobacteria, Bacteroidetes, and Verrucomicrobiota. The root endophytic Proteobacteria and Acidobacteria were significantly higher in abundance (p < 0.05) in the IMS than in the TMS, while Actinobacteria and Firmicutes were significantly lower in abundance. Five taxa were assigned to Proteobacteria and Acidobacteria, which were identified as keystones in the rhizosphere soil microbiome, while two species taxonomically affiliated with Proteobacteria were identified as keystones in the root endophytic microbiota, indicating this phylum can be an indicator for a root-associated microbiome in response to IMS. The soil pH, soil total organic carbon (TOC), total nitrogen (TN), total phosphorus (TP), available potassium (AK), and TOC:TP ratio were significantly correlated (p < 0.05) with the bacterial community composition of both rhizosphere soils and root endophytes. TMS increased the microbial network complexity of root endophytes but decreased the microbial network complexity of rhizosphere soil. Our results suggest IMS shapes the rhizosphere and endophytic bacterial community compositions and their interactions differently, which should be paid attention to when designing management practices for the sustainable development of forest ecosystems.
Language	English
Publishing date	2022-08-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704341-1
ISSN	2223-7747
ISSN	2223-7747
DOI	10.3390/plants11162129
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Article: Biochar-based organic fertilizer application rates for Tetrastigma hemsleyanum planted under Moso bamboo

Zhang, Xiaoping / Gao, Guibin / Wu, Zhizhuang / Wen, Xing / Bian, Fangyuan / Yang, Chuanbao

Journal of forestry research. 2020 Oct., v. 31, no. 5

2020

Abstract: The under-forest economy has received increased attention in China. However, little is known about the effects of co-composted biochar on soil and plant biomass in under-forest planting systems. In this study, plant biomass, soil nutrient levels, and ... ...

Abstract	The under-forest economy has received increased attention in China. However, little is known about the effects of co-composted biochar on soil and plant biomass in under-forest planting systems. In this study, plant biomass, soil nutrient levels, and bacterial communities were evaluated after application of biochar-based organic fertilizer (BOF, derived from co-composted biochar-compost) at varying rates to soils supporting Tetrastigma hemsleyanum Diels & Gilg planted under a Moso bamboo (Phyllostachys edulis) forest. BOF treatment increased the biomass of T. hemsleyanum. Compared with the control, BOF application significantly increased soil pH and organic carbon (SOC). The high-throughput sequencing results showed significant differences in the Bacteroidetes, Verrucomicrobia, Chlorofexi, and OD1 phyla among all groups. At the genus level, the control group was characterized by a preponderance of Conexibacter. Rhodanobacter was enriched in soils with a 3% BOF application and Steroidobacter and Spirochaeta were the most prominent phyla in the 5% BOF group. There was no biomarker selected in the 1% BOF group at the genus level. In conclusion, BOF application increased the biomass of T. hemsleyanum when intercropped under a Moso bamboo forest; this effect may be due to changes in the soil physicochemical properties and microbial communities after BOF application.
Keywords	Bacteroidetes ; Phyllostachys edulis ; Rhodanobacter ; Spirochaeta ; Tetrastigma ; Verrucomicrobia ; bacterial communities ; biochar ; biomarkers ; fertilizer rates ; forests ; high-throughput nucleotide sequencing ; intercropping ; nutrient content ; organic carbon ; organic fertilizers ; phytomass ; planting ; soil nutrients ; soil pH ; soil physical properties ; China
Language	English
Dates of publication	2020-10
Size	p. 1813-1821.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	2299615-1
ISSN	1993-0607 ; 1007-662X
ISSN (online)	1993-0607
ISSN	1007-662X
DOI	10.1007/s11676-019-00965-2
Database	NAL-Catalogue (AGRICOLA)

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Article: Highly bioactive iridium metal-complex alleviates spinal cord injury via ROS scavenging and inflammation reduction

Ji, Zhi-Sheng / Gao, Gui-Bin / Ma, Yan-Ming / Luo, Jian-Xian / Zhang, Guo-Wei / Yang, Hua / Li, Nan / He, Qing-Yu / Lin, Hong-Sheng

Biomaterials. 2022 May, v. 284

2022

Abstract: Generation of a promising antioxidative reagent with superior biocompatibility is urgently needed to remedy spinal cord injuries (SCI), repair the damaged neurons and restrain the secondary injuries caused by inflammation-induced oxidative stress. ... ...

Abstract	Generation of a promising antioxidative reagent with superior biocompatibility is urgently needed to remedy spinal cord injuries (SCI), repair the damaged neurons and restrain the secondary injuries caused by inflammation-induced oxidative stress. Inhibitory elements in the injury sites and necessitous inherent neural regeneration ability were major challenges for functional recovery after spinal cord injuries. We here developed a highly bioactive iridium complex (IrFPHtz) with enhanced antioxidative activities and improved SCI therapeutic efficacy. Both in vivo and in vitro, IrFPHtz has exhibited neuroprotective and anti-inflammatory properties. Mechanically, IrFPHtz directly targets SOD1 and upregulates the expression of SOD1 to eliminate the excess Reactive Oxygen Species (ROS) production induced by SCI, and thus protecting neuron cells from further damage. As a result, IrFPHtz safeguarded the neurons and myelin sheaths against trauma, lessened glial scar conformations and facilitated the repair of neurons and long axon expansion in the glial scar. Furthermore, IrFPHtz significantly ameliorated the behavioral functions of SCI mice and promoted a satisfactory curative effect. Therefore, this study sheds light on a novel method for SCI treatment using IrFPHtz as a potential drug and implicates the clinical significance of metal complexes in diseases featuring with upregulated ROS species.
Keywords	animal injuries ; axons ; biocompatibility ; biocompatible materials ; drugs ; inflammation ; iridium ; myelin sheath ; oxidative stress ; spinal cord ; therapeutics
Language	English
Dates of publication	2022-05
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2022.121481
Database	NAL-Catalogue (AGRICOLA)

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Article: Responses of soil nutrients and microbial communities to intercropping medicinal plants in moso bamboo plantations in subtropical China

Zhang, Xiaoping / Bian, Fangyuan / Gai, Xu / Gao, Guibin / Wen, Xing / Wu, Zhizhuang / Yang, Chuanbao / Zhong, Hao / Zhong, Zhezhe

Environmental science and pollution research international. 2020 Jan., v. 27, no. 2

2020

Abstract: Bamboo forests are one of the most important forest resources in subtropical China. A pure, single-layer bamboo forest is considered an optimal habitat for intercropping medicinal herbs. Soil microorganisms have an important role in various ecological ... ...

Abstract	Bamboo forests are one of the most important forest resources in subtropical China. A pure, single-layer bamboo forest is considered an optimal habitat for intercropping medicinal herbs. Soil microorganisms have an important role in various ecological processes and respond quickly to environmental changes. However, changes in soil nutrients and microbial communities associated with agroforestry cultivation methods remain poorly documented. In the present study, a pure moso bamboo (Phyllostachys edulis) forest (Con) and three adjacent moso bamboo–based agroforestry (BAF) systems (moso bamboo–Paris polyphylla (BP), moso bamboo–Tetrastigma hemsleyanum (BT) and moso bamboo–Bletilla striata (BB)) were selected; and their soil chemical properties and bacterial communities were studied and compared to evaluate the effects of agroforestry on soil bacterial communities and the relationship between soil properties and bacterial communities in BAF systems. Results showed that compared with soils under the Con, soils under the BAF systems had more (p < 0.05) soil organic carbon (SOC) and available nitrogen (AN) but lower (p < 0.05) pH and available potassium (AK). In addition, compared with the Con system, the BB and BT systems had significantly greater (p < 0.05) available phosphorus (AP). Compared with that in the Con system, the Shannon index in the BAF systems was significantly greater (p < 0.05), but the Chao1 index not different. On the basis of relative abundance values, compared with the Con soils, the BAF soils had a significantly greater abundance of (p < 0.05) Bacteroidetes and Planctomyces but a significantly lower abundance of (p < 0.05) Verrucomicrobia, Gemmatimonadetes and Candidatus Xiphinematobacter. Moreover, compared with the Con system, the BB and BT systems had a greater (p < 0.05) abundance of Actinobacteria, Rhodoplanes, Candidatus Solibacter and Candidatus Koribacter. Redundancy analysis (RDA) revealed that soil pH, SOC and AP were significantly correlated with bacterial community composition. Results of this study suggest that intercropping medicinal herbs can result in soil acidification and potassium (K) depletion; thus, countermeasures such as applications of K fertilizer and alkaline soil amendments are necessary for BAF systems.
Keywords	Actinobacteria ; agroforestry ; alkaline soils ; bacterial communities ; Bacteroidetes ; bamboos ; community structure ; forest resources ; forests ; Gemmatimonadetes ; habitats ; intercropping ; medicinal plants ; nitrogen ; phosphorus ; Phyllostachys edulis ; Planctomyces ; plantations ; potassium ; potassium fertilizers ; Rhodoplanes ; soil acidification ; soil amendments ; soil bacteria ; soil nutrients ; soil organic carbon ; soil pH ; Verrucomicrobia ; China
Language	English
Dates of publication	2020-01
Size	p. 2301-2310.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-019-06750-2
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Polyphyllin D punctures hypertrophic lysosomes to reverse drug resistance of hepatocellular carcinoma by targeting acid sphingomyelinase.

Wang, Yang / Chen, Yan-Yan / Gao, Gui-Bin / Zheng, Yang-Han / Yu, Nan-Nan / Ouyang, Lan / Gao, Xuejuan / Li, Nan / Wen, Shi-Yuan / Huang, Shangjia / Zhao, Qian / Liu, Langxia / Cao, Mingrong / Zhang, Shuixing / Zhang, Jing / He, Qing-Yu

Molecular therapy : the journal of the American Society of Gene Therapy

2023 Volume 31, Issue 7, Page(s) 2169–2187

Abstract: Hypertrophic lysosomes are critical for tumor progression and drug resistance; however, effective and specific lysosome-targeting compounds for cancer therapy are lacking. Here we conducted a lysosomotropic pharmacophore-based in silico screen in a ... ...

Abstract	Hypertrophic lysosomes are critical for tumor progression and drug resistance; however, effective and specific lysosome-targeting compounds for cancer therapy are lacking. Here we conducted a lysosomotropic pharmacophore-based in silico screen in a natural product library (2,212 compounds), and identified polyphyllin D (PD) as a novel lysosome-targeted compound. PD treatment was found to cause lysosomal damage, as evidenced by the blockade of autophagic flux, loss of lysophagy, and the release of lysosomal contents, thus exhibiting anticancer effects on hepatocellular carcinoma (HCC) cell both in vitro and in vivo. Closer mechanistic examination revealed that PD suppressed the activity of acid sphingomyelinase (SMPD1), a lysosomal phosphodieserase that catalyzes the hydrolysis of sphingomyelin to produce ceramide and phosphocholine, by directly occupying its surface groove, with Trp148 in SMPD1 acting as a major binding residue; this suppression of SMPD1 activity irreversibly triggers lysosomal injury and initiates lysosome-dependent cell death. Furthermore, PD-enhanced lysosomal membrane permeabilization to release sorafenib, augmenting the anticancer effect of sorafenib both in vivo and in vitro. Overall, our study suggests that PD can potentially be further developed as a novel autophagy inhibitor, and a combination of PD with classical chemotherapeutic anticancer drugs could represent a novel therapeutic strategy for HCC intervention.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/pathology ; Sorafenib/pharmacology ; Sphingomyelin Phosphodiesterase/pharmacology ; Liver Neoplasms/metabolism ; Lysosomes/metabolism ; Autophagy ; Drug Resistance ; Punctures
Chemical Substances	Sorafenib (9ZOQ3TZI87) ; polyphyllin D ; Sphingomyelin Phosphodiesterase (EC 3.1.4.12)
Language	English
Publishing date	2023-05-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2023.05.015
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Zs.A 5640: Show issues

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Article: Effects of key growth conditions on endogenous hormone content in tillering stem bases, germination of lateral buds, and biomass allocation in Indocalamus decorus

Gao, Guibin / Hao Zhong / Liangru Wu / Neng Li / Yanhong Pan / Zheke Zhong / Zhizhuang Wu

Journal of forestry research. 2018 Nov., v. 29, no. 6

2018

Abstract: Physiological responses and changes in growth of Indocalamus decorus Q.H.Dai under different ecological conditions are essential for further understanding growth regulation and adaptive mechanisms and establishing an evidence-based management system for ... ...

Abstract	Physiological responses and changes in growth of Indocalamus decorus Q.H.Dai under different ecological conditions are essential for further understanding growth regulation and adaptive mechanisms and establishing an evidence-based management system for optimal growth. In this study, the endogenous hormone content in tillering stem bases, germination of lateral buds, and biomass allocation of this bamboo species in different growth environments were investigated. Among the endogenous hormones in the basal stems of tillers, indole-3-pyruvic acid and zeatin riboside were highly correlated with lateral buds that germinated to form shoots, while gibberellic acid was highly correlated with lateral buds that germinated to form rhizomes. The best lateral bud germination characteristics were achieved with full sun, a density of six plantlets per pot, and watering every 6 days. I. decorus plantlets used different resource allocation strategies depending on treatment. Different ecological factors influenced endogenous hormones in the bamboo stem base, which affected lateral bud germination and biomass allocation.
Keywords	bamboos ; buds ; dry matter partitioning ; environmental factors ; germination ; gibberellic acid ; hormones ; physiological response ; plantlets ; resource allocation ; rhizomes ; shoots ; tillering ; tillers ; zeatin
Language	English
Dates of publication	2018-11
Size	p. 1547-1555.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	2299615-1
ISSN	1993-0607 ; 1007-662X
ISSN (online)	1993-0607
ISSN	1007-662X
DOI	10.1007/s11676-017-0577-2
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Article ; Online: Targeting ARF1-IQGAP1 interaction to suppress colorectal cancer metastasis and vemurafenib resistance.

Hu, Hui-Fang / Gao, Gui-Bin / He, Xuan / Li, Yu-Ying / Li, Yang-Jia / Li, Bin / Pan, YunLong / Wang, Yang / He, Qing-Yu

Journal of advanced research

2022 Volume 51, Page(s) 135–147

Abstract: Introduction: Acquired resistance to BRAF inhibitor vemurafenib is frequently observed in metastatic colorectal cancer (CRC), and it is a thorny issue that results in treatment failure. As adaptive responses for vemurafenib treatment, a series of ... ...

Abstract	Introduction: Acquired resistance to BRAF inhibitor vemurafenib is frequently observed in metastatic colorectal cancer (CRC), and it is a thorny issue that results in treatment failure. As adaptive responses for vemurafenib treatment, a series of cellular bypasses are response for the adaptive feedback reactivation of ERK signaling, which warrant further investigation. Objectives: We identified ARF1 (ADP-ribosylation factor 1) as a novel regulator of both vemurafenib resistance and cancer metastasis, its molecular mechanism and potential inhibitor were investigated in this study. Methods: DIA-based quantitative proteomics and RNA-seq were performed to systematic analyze the profiling of vemurafenib-resistant RKO cells (RKO-VR) and highly invasive RKO cells (RKO-I8), respectively. Co‑immunoprecipitation assay was performed to detect the interaction of ARF1 and IQGAP1 (IQ-domain GTPase activating protein 1). An ELISA-based drug screen system on FDA-approved drug library was established to screen the compounds against the interaction of ARF1-IQGAP1.The biological functions of ARF1 and LY2835219 were determined by transwell, western blotting, Annexin V-FITC/PI staining and in vivo experimental metastasis assays. Results: We found that ARF1 strongly interacted with IQGAP1 to activate ERK signaling in VR and I8 CRC cells. Deletion of IQGAP1 or inactivation of ARF1 (ARF-T48S) restored the invasive ability induced by ARF1. As ARF1-IQGAP1 interaction is essential for ERK activation, we screened LY2835219 as novel inhibitor of ARF1-IQGAP1 interaction, which inactivated ERK signaling and suppressed CRC metastasis and vemurafenib-resistance in vitro and in vivo with no observed side effect. Furthermore, LY2835219 in combined treatment with vemurafenib exerted significantly inhibitory effect on ARF1-mediated cancer metastasis than used independently. Conclusion: This study uncovers that ARF1-IQGAP1 interaction-mediated ERK signaling reactivation is critical for vemurafenib resistance and cancer metastasis, and that LY2835219 is a promising therapeutic agent for CRC both as a single agent and in combination with vemurafenib.
MeSH term(s)	Humans ; Vemurafenib/pharmacology ; Vemurafenib/therapeutic use ; ADP-Ribosylation Factor 1 ; Cell Line, Tumor ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology
Chemical Substances	Vemurafenib (207SMY3FQT) ; IQ motif containing GTPase activating protein 1 ; abemaciclib (60UAB198HK) ; ADP-Ribosylation Factor 1 (EC 3.6.5.2)
Language	English
Publishing date	2022-11-14
Publishing country	Egypt
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541849-X
ISSN	2090-1224 ; 2090-1224
ISSN (online)	2090-1224
ISSN	2090-1224
DOI	10.1016/j.jare.2022.11.006
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