Pre-clinical and clinical importance of miR-21 in human cancers: Tumorigenesis, therapy response, delivery approaches and targeting agents

Hashemi, Mehrdad; Mirdamadi, Motahare Sadat Ayat; Talebi, Yasmin; Khaniabad, Nasrin; Banaei, Gooya; Daneii, Pouria; Gholami, Sadaf; Ghorbani, Amin; Tavakolpournegari, Alireza; Farsani, Zoheir Mohammadian; Zarrabi, Ali; Nabavi, Noushin; Zandieh, Mohammad Arad; Rashidi, Mohsen; Taheriazam, Afshin; Entezari, Maliheh; Khan, Haroon

doi:10.1016/j.phrs.2022.106568

Cited by 29 publications

(9 citation statements)

References 288 publications

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“…Interestingly, elevated concentrations of miRNA-21 can indirectly induce resistance to chemotherapy by facilitating hypoxia, a state that aids tumors in evading the immune system, fostering resistance to chemotherapy, and activating many processes that impact tumor formation. Hypoxia induces the activation of hypoxia-inducible factor HIF-1α, which subsequently promotes the synthesis of miRNA-21 (Hashemi et al 2023). Cancer cells are able to avoid the reduction in cell division caused by hypoxia by escaping apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Functionalized siRNA-chitosan nanoformulations promote triple-negative breast cancer cell death via blocking the miRNA-21/AKT/ERK signaling axis: in-silico and in vitro studies

Abdulmalek,

Saleh,

Shahin

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Oncogenic microRNA (miRNA), especially miRNA-21 upregulation in triple-negative breast cancer (TNBC), suggests a new class of therapeutic targets. In this study, we aimed to create GE11 peptide-conjugated small interfering RNA-loaded chitosan nanoparticles (GE11-siRNA-CSNPs) for the targeting of EGFR overexpressed TNBC and selectively inhibit miRNA-21 expression. A variety of in-silico and in vitro cellular and molecular studies were conducted to investigate the binding affinities of specific targets used as well as the anticancer efficacies and mechanisms of GE11-siRNA-CSNPs in TNBC cells. An in-silico assessment reveals a distinct binding affinity of miRNA-21 with siRNA as well as between the extracellular domain of EGFR and synthesized peptides. Notably, the in vitro results showed that GE11-siRNA-CSNPs were revealed to have better cytotoxicity against TNBC cells. It significantly inhibits miRNA-21 expression, cell migration, and colony formation. The results also indicated that GE11-siRNA-CSNPs impeded cell cycle progression. It induces cell death by reducing the expression of the antiapoptotic gene Bcl-2 and increasing the expression of the proapoptotic genes Bax, Caspase 3, and Caspase 9. Additionally, the docking analysis and immunoblot investigations verified that GE1-siRNA-CSNPs, which specifically target TNBC cells and suppress miRNA-21, can prevent the effects of miRNA-21 on the proliferation of TNBC cells via controlling EGFR and subsequently inhibiting the PI3K/AKT and ERK1/2 signaling axis. The GE11-siRNA-CSNPs design, which specifically targets TNBC cells, offers a novel approach for the treatment of breast cancer with improved effectiveness. This study suggests that GE11-siRNA-CSNPs could be a promising candidate for further assessment as an additional strategy in the treatment of TNBC. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Functionalized siRNA-chitosan nanoformulations promote triple-negative breast cancer cell death via blocking the miRNA-21/AKT/ERK signaling axis: in-silico and in vitro studies

Abdulmalek,

Saleh,

Shahin

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Cancer cells manage to avoid the destroy of intrinsic or extrinsic apoptosis through vary mechanisms [ 109 ]. The findings that exosomes derived from TAM hold the capacity to suppress cell apoptosis and enhance activation of PI3K/AKT signaling pathway by down-regulation of PTEN via transfer of miR-21 had shed new lights on role of exosome in resistance to apoptosis [ 110 , 111 ]. The tRNA-derived fragments (tRFs) are a novel class of small non-coding ribonucleic acids (ncRNAs) derived from precursors or mature tRNAs, and their biological functions have received much attention in recent years [ 112 ].…”

Section: Tumor Biology Of Exosomesmentioning

confidence: 99%

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

Wu,

Cao,

Chen

et al. 2024

Biol Proced Online

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Exosomes are increasingly recognized as important mediators of intercellular communication in cancer biology. Exosomes can be derived from cancer cells as well as cellular components in tumor microenvironment. After secretion, the exosomes carrying a wide range of bioactive cargos can be ingested by local or distant recipient cells. The released cargos act through a variety of mechanisms to elicit multiple biological effects and impact most if not all hallmarks of cancer. Moreover, owing to their excellent biocompatibility and capability of being easily engineered or modified, exosomes are currently exploited as a promising platform for cancer targeted therapy. In this review, we first summarize the current knowledge of roles of exosomes in risk and etiology, initiation and progression of cancer, as well as their underlying molecular mechanisms. The aptamer-modified exosome as a promising platform for cancer targeted therapy is then briefly introduced. We also discuss the future directions for emerging roles of exosome in tumor biology and perspective of aptamer-modified exosomes in cancer therapy.

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“…However, anti-cancer drugs like doxorubicin can paradoxically upregulate miR-21 through NF-kappa B activation, promoting breast cancer progression ( O’Bryan et al, 2017 ). Nevertheless, targeting miR-21 in cancer therapy has shown increased sensitivity to anti-cancer agents in breast cancer ( Hashemi et al, 2023 ).…”

Section: Disease Associations In Cancer (Oncomirs)mentioning

confidence: 99%

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies

Abdul Manap,

Wisham,

Wong

et al. 2024

Front. Cell Dev. Biol.

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Among women, breast cancer ranks as the most prevalent form of cancer, and the presence of metastases significantly reduces prognosis and diminishes overall survival rates. Gaining insights into the biological mechanisms governing the conversion of cancer cells, their subsequent spread to other areas of the body, and the immune system’s monitoring of tumor growth will contribute to the advancement of more efficient and targeted therapies. MicroRNAs (miRNAs) play a critical role in the interaction between tumor cells and immune cells, facilitating tumor cells’ evasion of the immune system and promoting cancer progression. Additionally, miRNAs also influence metastasis formation, including the establishment of metastatic sites and the transformation of tumor cells into migratory phenotypes. Specifically, dysregulated expression of these genes has been associated with abnormal expression of oncogenes and tumor suppressor genes, thereby facilitating tumor development. This study aims to provide a concise overview of the significance and function of miRNAs in breast cancer, focusing on their involvement as tumor suppressors in the antitumor immune response and as oncogenes in metastasis formation. Furthermore, miRNAs hold tremendous potential as targets for gene therapy due to their ability to modulate specific pathways that can either promote or suppress carcinogenesis. This perspective highlights the latest strategies developed for miRNA-based therapies.

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Pre-clinical and clinical importance of miR-21 in human cancers: Tumorigenesis, therapy response, delivery approaches and targeting agents

Cited by 29 publications

References 288 publications

Functionalized siRNA-chitosan nanoformulations promote triple-negative breast cancer cell death via blocking the miRNA-21/AKT/ERK signaling axis: in-silico and in vitro studies

Functionalized siRNA-chitosan nanoformulations promote triple-negative breast cancer cell death via blocking the miRNA-21/AKT/ERK signaling axis: in-silico and in vitro studies

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies

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