MSC-Derived exosomes suppress colorectal cancer cell proliferation and metastasis via miR-100/mTOR/miR-143 pathway

Jahangiri, Babak; Khalaj‐Kondori, Mohammad; Asadollahi, Elahe; Dizaj, Leyli Purrafee; Majid, Shahana

doi:10.1016/j.ijpharm.2022.122214

Cited by 37 publications

(30 citation statements)

References 66 publications

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“…These ndings show that miR-99a exerts its anticancer effects in human cancer cells by targeting the mTOR/p-4E-BP1/pS6K1 pathway. It has also been demonstrated that miR-143 can inhibit the Akt/mTOR pathway [33,34]. Moreover, miR-143 targets KRAS by binding to distinct regions in its 3′ UTR, and it inhibits the effector signal molecules AKT and ERK, which are downstream molecules of PI3K and Raf [35].…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of miR-143 with miR-99a inhibited cell proliferation and induced apoptosis in breast cancer

Doosti

Ebrahimi

Ghahfarokhi

et al. 2023

Preprint

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Introduction: Breast cancer (BC) is the most common cancer type and the fifth leading cause of cancer-related death. The primary goals of BC treatment are to remove the tumor and prevent metastasis. Despite advances in BC treatment, more effective therapies are required. miRNAs can regulate many targets involved in biological processes and tumor progression; these molecules have emerged as a promising cancer treatment strategy. In the present study, we investigated the effects of miR-99a and miR-143 in based single expression plasmids for BC inhibition. Methods: In this study, the precursor structure of miRNAs in the expression vector pEGFP-N1 entered single and double states, and MCF7 and T47D cells were transfected. The miRNAs expression level after transfection was then measured using qPCR. The MultiMiR package was used to obtain predicted and validated miRNA targets. MTT assay, qRT-PCR, migration test, and flow cytometry were used to assess the effect of miRNA and gene modulation. Results: The qPCR results revealed that miRNA constructs were significantly expressed after the transfection of both cell lines. The biological function of miRNAs showed that upregulation of miR-99a and miR-143 in any of the two selected BC cells inhibited their proliferation and migration rate, significantly inducing apoptosis (p<0.01). Also, miR-99a/-143 co-treatment has a synergistic anticancer effect in cancer cells via Akt1 and CDK6 targeting. Conclusion: These findings suggest that miR-99a/-143 plays synergistic regulatory roles in BC, possibly via a shared signaling pathway, providing a therapeutic strategy for BC treatment.

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Section: Discussionmentioning

confidence: 99%

Synergistic effects of miR-143 with miR-99a inhibited cell proliferation and induced apoptosis in breast cancer

Doosti

Ebrahimi

Ghahfarokhi

et al. 2023

Preprint

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“…By pairing to the mRNAs of protein-coding genes, miRNAs play an important role in regulating post-transcriptional silencing of target genes [58,59]. There is accumulating evidence that miRNAs are enriched in MSC-EXO and are the major bioactive constituents [60][61][62]. In the last few decades, the cardioprotective role of MSC-derived exosomal miRNAs has attracted huge attention [63].…”

Section: Exosomal Mirnas In Msc-exo For MI Treatmentmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes for Myocardial Infarction Treatment

Zheng¹,

Hong²,

Hu³

et al. 2023

Exosomes - Recent Advances From Bench to Bedside

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Myocardial infarction (MI) is a major cause of morbidity and mortality in modern society. Over the past decades, mesenchymal stem cell (MSCs)-based therapy has shown promising results in the treatment of MI due to their unique properties of multi-differentiation ability, immune-privileged phenotype and paracrine activity. Recently, MSC-derived exosomes (MSC-EXO) have been proposed as a promising therapeutic strategy for MI with their ability to inhibit cardiomyocyte apoptosis and stimulate vascular angiogenesis. They also aid immunoregulation and rejuvenation of cardiomyocyte senescence by transporting their unique content such as proteins, lipids, and miRNAs. Compared with MSC transplantation, MSC-EXO administration has shown several advantages, including lower toxicity and immunogenicity and no risk of tumor formation. Nonetheless the potential mechanisms underlying MSC-EXO-based therapy for MI are not fully understood. In addition, lack of modification of MSC-EXOs can impact therapeutic efficacy. It is vital to optimize MSC-EXO and enhance their therapeutic efficacy for MI. We summarize the recent advances regarding biological characteristics, therapeutic potential and mechanisms, and optimal approaches to the use of MSC-EXOs in the treatment of MI.

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“…In regards to the ultracentrifugation method of exosome isolation, there are several disadvantages, including: there is a great deal of labor and time involved in this method; the structure of ultracentrifuge rotors has restrictions that prevent processing more than six samples at once; and exosome yields are often poor. Sequential centrifugations, however, can result in high‐purity exosome preparations when paired with sucrose gradient ultracentrifugation, and several researchers have employed this technique for exosome extraction effectively over the past ten years (Jahangiri et al 2022; Lai et al 2010; Liu et al 2022; Yakubovich et al 2022). Using this procedure, Yang et al (2020) isolated and purified intestinal exosomes for autologous exosome transfer in a colitis murine model.…”

Section: Exosomes: Biogenesis Structure Isolation and Characterizationmentioning

confidence: 99%

“…The tumor‐promoting impact of EMT‐induced transcription factors might be inhibited by miR‐100 elevated levels. Furthermore, our recent study showed that the hBM‐MSC‐exosomal miR‐100 and miR‐143 may inhibit cell proliferation and trigger apoptosis in colorectal cancer (CRC) cells through the miR‐100/mTOR/miR‐143 axis (Jahangiri et al 2022). Moreover, it was shown that miR‐16 reduced the expression of VEGF (Dejean et al 2011).…”

Section: Msc‐exos and Tumor Proliferationmentioning

confidence: 99%

“…According to research by Lee et al, the miR‐145 and miR‐124 delivered by MSC‐Exos strongly inhibit glioma cell migration and glioma stem cell self‐renewal (Lee et al 2013a). By delivering miR‐143 through MSC‐Exos, it is possible to alter the biological functions of osteosarcoma and CRC cells as well as decrease their ability for migration (Jahangiri et al 2022; Shimbo, et al 2014). As a case in point, the use of BM‐MSC‐Exos in conjunction with radiation therapy has the ability to significantly enhance tumor cell death and decrease metastatic tumor foci, indicating its potential therapeutic efficacy in anti‐metastatic treatment (Araujo Farias et al 2018).…”

Section: Msc‐exos In Cancer Metastasis and Emtmentioning

confidence: 99%

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Dual impacts of mesenchymal stem cell-derived exosomes on cancer cells: unravelling complex interactions

Jahangiri,

Khalaj-Kondori,

Asadollahi

et al. 2023

J. Cell Commun. Signal.

Self Cite

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Mesenchymal stem cells (MSCs) are multipotent, self-renewing stromal cells found in a variety of adult tissues. MSCs possess a remarkable ability to migrate towards tumor sites, known as homing. This homing process is mediated by various factors, including chemokines, growth factors, and extracellular matrix components present in the tumor microenvironment. MSCs release extracellular vesicles known as exosomes (MSC-Exos), which have been suggested to serve a key role in mediating a wide variety of MSC activities. Through cell-cell communication, MSC-Exos have been shown to alter recipient cell phenotype or function and play as a novel cell-free alternative for MSC-based cell therapy. However, MSC recruitment to tumors allows for their interaction with cancer cells and subsequent regulation of tumor behavior. MSC-Exos act as tumor niche modulators via transferring exosomal contents, such as specific proteins or genetic materials, to the nearby cancer cells, leading to either promotion or suppression of tumorigenesis, angiogenesis, and metastasis, depending on the specific microenvironmental cues and recipient cell characteristics. Consequently, there is still a debate about the precise relationship between tumor cells and MSC-Exos, and it is unclear how MSC-Exos impacts tumor cells. Although the dysregulation of miRNAs is caused by the progression of cancer, they also play a direct role in either promoting or inhibiting tumor growth as they act as either oncogenes or tumor suppressors. The utilization of MSC-Exos may prove to be an effective method for restoring miRNA as a means of treating cancer. This review aimed to present the existing understanding of the impact that MSC-Exos could have on cancer. To begin with, we presented a brief explanation of exosomes, MSCs, and MSC-Exos. Following this, we delved into the impact of MSC-Exos on cancer growth, EMT, metastasis, angiogenesis, resistance to chemotherapy and radiotherapy, and modulation of the immune system.

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MSC-Derived exosomes suppress colorectal cancer cell proliferation and metastasis via miR-100/mTOR/miR-143 pathway

Cited by 37 publications

References 66 publications

Synergistic effects of miR-143 with miR-99a inhibited cell proliferation and induced apoptosis in breast cancer

Synergistic effects of miR-143 with miR-99a inhibited cell proliferation and induced apoptosis in breast cancer

Mesenchymal Stem Cell-Derived Exosomes for Myocardial Infarction Treatment

Dual impacts of mesenchymal stem cell-derived exosomes on cancer cells: unravelling complex interactions

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