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Last update 08 May 2025

MIA

Last update 08 May 2025

Basic Info

Synonyms

CD-RAP, Melanoma inhibitory activity protein, Melanoma-derived growth regulatory protein

+ [2]

Introduction

Elicits growth inhibition on melanoma cells in vitro as well as some other neuroectodermal tumors, including gliomas.

Drugs associated with MIA

ST-05

Target

MIA

Mechanism

MIA stimulators

Active Org.-

Originator Org.

BioNet Pharma GmbH

Active Indication-

Inactive Indication

Spinal Diseases

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MIA

100 Translational Medicine associated with MIA

0 Patents (Medical) associated with MIA

570

Literatures (Medical) associated with MIA

28 Mar 2025·Plant Physiology

Three Rho of Plant (ROP)-GTPase regulatory proteins control ROP-mediated alkaloid biosynthesis in Catharanthus roseus

Article

Author: Parihar, Durgesh ; Sharma, Anuj ; Gupta, Priyanka ; Nagegowda, Dinesh A ; Mohan, Sruthi

AbstractRho of plant (ROP)-GTPase regulatory proteins (RGRPs) have been shown to control plant morphogenesis, development, and immunity; however, their role in specialized metabolism remains unknown. Here, we demonstrate that specific RGRPs control monoterpene indole alkaloid (MIA) biosynthesis by interacting with distinct ROPs in Madagascar periwinkle (Catharanthus roseus). Among the 5 guanine nucleotide exchange factors (GEFs), 4 GTPase-activating proteins (GAPs), and 2 GDP dissociation inhibitors (GDIs) identified in the C. roseus genome, only CrGEF1, CrGAP1, and CrGDI2 specifically interacted with CrROP3 and CrROP5. These RGRPs displayed distinct cytosolic and/or membrane localization patterns, with their transcripts predominantly expressed in aerial tissues. Functional studies revealed that CrGEF1 acts as a positive regulator of MIA biosynthesis, as silencing its gene led to a reduction in MIA production, while overexpression enhanced MIA levels. Conversely, CrGAP1 and CrGDI2 function as negative regulators, with silencing resulting in increased MIA production and overexpression causing reduced MIA levels. Notably, terminal truncated forms of these RGRPs showed interaction with CrROP3 or CrROP5 but failed to influence MIA biosynthesis, underscoring the importance of these domains in their regulatory functions. Overall, our findings uncover a mechanism by which distinct RGRPs coordinate with specific ROPs to regulate transcription factors and fine-tune MIA biosynthesis in C. roseus.

01 Mar 2025·Journal of Genetic Engineering and Biotechnology

Exploration of crucial stromal risk genes associated with prognostic significance and chemotherapeutic opportunities in invasive ductal breast carcinoma

Article

Author: Tang, Guohua ; Zhang, Yang ; Geng, Wei ; Yu, Yang ; Wang, Zhi

BACKGROUNDFew studies revealed that stromal genes regulate the tumor microenvironment (TME). However, identification of key-risk genes in the invasive ductal breast carcinoma-associated stroma (IDBCS) and their associations with the prediction of risk group remains lacking.METHODSThis study used the GSE9014, GSE10797, GSE8977, GSE33692, and TGGA BRCA datasets. We explored the differentially expressed transcriptional markers, hub genes, gene modules, and enriched KEGG pathways. We employed a variety of algorithms, such as the log-rank test, the LASSO-cox model, the univariate regression model, and the multivariate regression model, to predict prognostic-risk genes and the prognostic-risk model. Finally, we employed a molecular docking-based study to explore the interaction of sensitive drugs with prognostic-risk genes.RESULTSIn comparing IDBCS and normal stroma, we discovered 1472 upregulated genes and 1400 downregulated genes (combined ES > 0585 and adjusted p-value < 0.05). The hub genes enrich cancer, immunity, and cellular signaling pathways. We explored the 12 key risk genes (ADAM8, CD86, CSRP1, DCTN2, EPHA1, GALNT10, IGFBP6, MIA, MMP11, RBM22, SLC39A4, and SYT2) in the IDBCS to identify the high-risk group and low-risk group patients. The high-risk group had a lower survival rate, and the constructed ROC curves evaluated the validity of the risk model. Expression validation and diagnostic efficacy revealed that the key stromal risk genes are consistently deregulated in the high-risk group and high stromal samples of the TCGA BRCA cohort. The expression of crucial risk genes, including CD86, CSRP1, EPHA1, GALNT10, IGFBP6, MIA, and RBM22 are associated with drug resistance and drug sensitivity. Finally, a molecular docking study explored several sensitive drugs (such as QL-XII-61, THZ-2-49, AZ628, NG-25, lapatinib, dasatinib, SB590885, and dabrafenib) interacted with these essential risk genes through hydrogen bonds and other chemical interactions.CONCLUSIONSExploring essential prognostic-risk genes and their association with the prognosis, diagnostic efficacy, and risk-group prediction may provide substantial clues for targeting the breast cancer stromal key-risk genes.

01 Feb 2025·Plant Physiology and Biochemistry

Harnessing the spatial and transcriptional regulation of monoterpenoid indole alkaloid metabolism in Alstonia scholaris leads to the identification of broad geissoschizine cyclase activities

Article

Author: Abbasi, Bilal Haider ; Méteignier, Louis-Valentin ; Koudounas, Konstantinos ; Beniddir, Mehdi A ; Delannoy, Etienne ; Pateyron, Stéphanie ; Birer Williams, Caroline ; Dutilleul, Christelle ; Oudin, Audrey ; Besseau, Sébastien ; Papon, Nicolas ; Lezin, Enzo ; Courdavault, Vincent ; Zamar, Duchesse-Lacours ; Sun, Chao ; Perrot, Thomas ; Lanoue, Arnaud ; Barunava, Patra ; Gautron, Nicolas ; Szwarc, Sarah ; Le Pogam, Pierre ; Brunaud, Veronique ; St-Pierre, Benoit ; Yuan, Ling ; Jensen, Michael Krogh ; Durand, Mickael

Monoterpene indole alkaloids (MIAs) are valuable metabolites produced in numerous medicinal plants from the Apocynaceae family such as Alstonia scholaris, which synthesizes strictamine, a MIA displaying neuropharmacological properties of a potential importance. To get insights into the MIA metabolism in A. scholaris, we studied here both the spatial and transcriptional regulations of MIA genes by performing a robust transcriptomics analysis of the main plant organs, leaf epidermis but also by sequencing RNA from leaves transiently overexpressing the master transcriptional regulator MYC2. These transcriptomic studies notably demonstrated that the first steps of the MIA pathway are successively distributed in the internal phloem associated parenchyma and epidermis, and that MYC2 exerts a remarkable transcriptional effect by modulating the expression of around 1000 genes. By combining these distinct datasets, we initiated the search for MIA-related genes encoding CYP71, based on the similarity of expression compared to already known MIA genes. Transient expression of these candidates in Nicotiana benthamiana leaves and yeast notably led to the identification of a related isoform of rhazimal synthase (RHS) capable of converting the MIA precursor geissoschizine into akuammicine, strictamine and 16-epi-pleiocarpamine. Investigating its catalytic mechanism revealed that strictamine results from rhazimal deformylation and that a similar mechanism may also explain 16-epi-pleiocarpamine synthesis. This prompted us to rename these enzymes geissoschizine cyclase due to their capacity of cyclizing geissoschizine into three different MIA scaffolds and to form both C-C and C-N bonds. This identification thus illustrates the potential of integrating spatial and transcriptional regulation analysis for MIA gene identification.

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