MicroRNA-494 induces breast cancer cell apoptosis and reduces cell viability by inhibition of nicotinamide phosphoribosyltransferase expression and activity

Ghorbanhosseini, Seyedeh Sara; Nourbakhsh, Mitra; Zangooei, Mohammad; Abdolvahabi, Zohreh; Bolandghamtpour, Zahra; Hesari, Zahra; Yousefi, Zeynab; Panahi, Ghodratollah; Meshkani, Reza

doi:10.17179/excli2018-1748

Cited by 8 publications

(6 citation statements)

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“…Marino and colleagues have published data that supports the role of miR-494-5p as a tumor suppressor using miR profiling conducted on breast cancer tissues [ 23 ]. Moreover, several other groups have shown that this miR acts as a tumor suppressor in human breast cancer tissues [ 24 , 95 , 96 ] or osteosarcoma [ 32 , 97 ].…”

Section: Discussionmentioning

confidence: 99%

JAK1 Is a Novel Target of Tumor- and Invasion-Suppressive microRNA 494-5p in Colorectal Cancer

Patil,

Abdelrahim,

Leupold

et al. 2023

Cancers

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MiR-494-5p expression has been suggested to be associated with colorectal cancer (CRC) and its metastases in our previous studies. However, functional investigations on the molecule-mediating actions of this miR in CRC are lacking. In silico analysis in the present study revealed a putative binding sequence within the 3′UTR of JAK1. Overexpression of miR-494-5p in cultured CRC significantly reduced the luciferase activity of a reporter plasmid containing the wild-type JAK1-3′UTR, which was abolished by seed sequence mutation. Furthermore, the overexpression of miR-494-5p in CRC cell lines led to a significant reduction in JAK1 expression, proliferation, in vitro migration, and invasion. These effects were abolished by co-transfection with a specific double-stranded RNA that inhibits endogenous miR-494-5p. Moreover, IL-4-induced migration, invasion, and phosphorylation of JAK1, STAT6, and AKT proteins were reduced after an overexpression of this miR, suggesting that this miR affects one of the most essential pathways in CRC. A Kaplan–Meier plotter analysis revealed that patients with high JAK1 expression show reduced survival. Together, these data suggest that miR-494-5p physically inhibits the expression of JAK1 at the translational level as well as in migration and invasion, supporting the hypothesis of miR-494-5p as an early tumor suppressor and inhibitor of early steps of metastasis in CRC.

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Section: Discussionmentioning

confidence: 99%

JAK1 Is a Novel Target of Tumor- and Invasion-Suppressive microRNA 494-5p in Colorectal Cancer

Patil,

Abdelrahim,

Leupold

et al. 2023

Cancers

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“…miR‐494 inhibits breast cancer progression by targeting PAK1 91 and inducing apoptosis. 92 miR‐22, a TS‐miR, inhibits breast cancer metastasis by targeting SIRT1 93 and inducing cellular senescence. 94 miR‐148a functions as TS of breast cancer metastasis 95 via inhibiting migration, invasion by targeting WNT‐1.…”

Section: Discussionmentioning

confidence: 99%

Curcumin alters distinct molecular pathways in breast cancer subtypes revealed by integrated miRNA/mRNA expression analysis

2022

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Background Curcumin is well known for its anticancer properties. Its cytotoxic activity has been documented in several cancer cell lines, including breast cancer. The pleiotropic activity of curcumin as an antioxidant, an antiangiogenic, antiproliferative, and pro‐apoptotic, is due to its diverse targets, such as signaling pathways, protein/enzyme, or noncoding gene. Aim This study aimed to identify key miRNAs and mRNAs induced by curcumin in breast cancer cells MCF7, T47D (hormone positive), versus MDA‐MB231 (hormone negative) using comparative analysis of global gene expression profiles. Methods RNA was isolated and subjected to mRNA and miRNA library sequencing to study the global gene expression profile of curcumin‐treated breast cancer cells. The differential expression of gene and miRNA was performed using the DESeq R package. The enriched pathways were studied using cluster profileR, and integrated miRNA–mRNA analysis was carried out using miRtarvis and miRmapper tools. Results Curcumin treatment led to upregulation of 59% TSGs in MCF7, 21% in MDA‐MB‐231 cells, and 36% TSGs in T47D, and downregulation of 57% oncogenes in MCF7, 76% in MDA‐MB‐231, and 91% in T47D. Similarly, curcumin treatment led to upregulation of 32% TSmiRs in MCF7, 37.5% in MDA‐MB231, and 62.5% in T47D, and downregulation of 77% oncomiRs in MCF7, 50% in MDA‐MB231 and 28.6% in T47D. Integrated analysis of miRNA–mRNA led to the identification of a common NFKB pathway altered by curcumin in all three cell lines. Analysis of uniquely enriched pathway revealed non‐integrin membrane–ECM interactions and laminin interactions in MCF7; extracellular matrix organization and degradation in MDA‐MB‐231 and cell cycle arrest and G2/M transition in T47D. Conclusion Curcumin regulates miRNA and mRNA in a cell type‐specific manner. The integrative analysis led to the detection of miRNAs and mRNAs pairs, which can be used as biomarkers associated with carcinogenesis, diagnostic, and treatment response in breast cancer.

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“…A recent study proposed that has-miR-494-3p was significantly altered in studied COVID-19 patients [36]. In addition, human miR-494 has been reported as a novel therapeutic marker for human breast cancer [86,87]. These findings suggest that bovine miR-494 could be a potential therapeutic marker against BCoV.…”

Section: Potential Role Of Mirnas As Biological Markers For Bcov Infe...mentioning

confidence: 92%

The Potential Roles of Host Cell miRNAs in Fine-Tuning Bovine Coronavirus (BCoV) Molecular Pathogenesis, Tissue Tropism, and Immune Regulation

Shah,

Hemida

2024

Microorganisms

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Bovine coronavirus (BCoV) infection causes significant economic loss to the dairy and beef industries worldwide. BCoV exhibits dual tropism, infecting the respiratory and enteric tracts of cattle. The enteric BCoV isolates could also induce respiratory manifestations under certain circumstances. However, the mechanism of this dual tropism of BCoV infection has not yet been studied well. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a dual role in virus infection, mediating virus or modulating host immune regulatory genes through complex virus–host cell interactions. However, their role in BCoV infection remains unclear. This study aims to identify bovine miRNAs crucial for regulating virus–host interaction, influencing tissue tropism, and explore their potential as biomarkers and therapeutic agents against BCoV. We downloaded 18 full-length BCoV genomes (10 enteric and eight respiratory) from GenBank. We applied several bioinformatic tools to study the host miRNAs targeting various regions in the viral genome. We used the criteria of differential targeting between the enteric/respiratory isolates to identify some critical miRNAs as biological markers for BCoV infection. Using various online bioinformatic tools, we also searched for host miRNA target genes involved in BCoV infection, immune evasion, and regulation. Our results show that four bovine miRNAs (miR-2375, miR-193a-3p, miR-12059, and miR-494) potentially target the BCoV spike protein at multiple sites. These miRNAs also regulate the host immune suppressor pathways, which negatively impacts BCoV replication. Furthermore, we found that bta-(miR-2338, miR-6535, miR-2392, and miR-12054) also target the BCoV genome at certain regions but are involved in regulating host immune signal transduction pathways, i.e., type I interferon (IFN) and retinoic acid-inducible gene I (RIG-I) pathways. Moreover, both miR-2338 and miR-2392 also target host transcriptional factors RORA, YY1, and HLF, which are potential diagnostic markers for BCoV infection. Therefore, miR-2338, miR-6535, miR-2392, and miR-12054 have the potential to fine-tune BCoV tropism and immune evasion and enhance viral pathogenesis. Our results indicate that host miRNAs play essential roles in the BCoV tissue tropism, pathogenesis, and immune regulation. Four bovine miRNAs (miR-2375, bta-miR-193a-3p, bta-miR-12059, and bta-miR-494) target BCoV-S glycoprotein and are potentially involved in several immune suppression pathways during the viral infection. These miRNA candidates could serve as good genetic markers for BCoV infection. However, further studies are urgently needed to validate these identified miRNAs and their target genes in the context of BCoV infection and dual tropism and as genetic markers.

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MicroRNA-494 induces breast cancer cell apoptosis and reduces cell viability by inhibition of nicotinamide phosphoribosyltransferase expression and activity

Cited by 8 publications

References 50 publications

JAK1 Is a Novel Target of Tumor- and Invasion-Suppressive microRNA 494-5p in Colorectal Cancer

JAK1 Is a Novel Target of Tumor- and Invasion-Suppressive microRNA 494-5p in Colorectal Cancer

Curcumin alters distinct molecular pathways in breast cancer subtypes revealed by integrated miRNA/mRNA expression analysis

The Potential Roles of Host Cell miRNAs in Fine-Tuning Bovine Coronavirus (BCoV) Molecular Pathogenesis, Tissue Tropism, and Immune Regulation

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