Development of MicroRNAs as Potential Therapeutics against Cancer

Abd‐Aziz, Noraini; Kamaruzman, Nur Izyani; Poh, Chit Laa

doi:10.1155/2020/8029721

Cited by 63 publications

(43 citation statements)

References 142 publications

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“…Over the past decade it has become clear that miRs are differentially expressed in many human malignancies [ 11 , 26 ] and associated with stage, progression, and metastasis of cancer [ 27 ]. Understanding the underlying mechanisms of miR dysregulation in malignant cells, that include chromosomal aberrations, changes in transcriptional control, epigenetic changes, and defects in the miR biogenesis pathway, is important to develop therapeutical anti-cancer strategies [ 28 ].…”

Section: Mechanisms Of Mir Dysregulation In the Tmementioning

confidence: 99%

“…In line with PEI, cationic dendrimers, consisting poly(amidoamine) (PAMAM) or poly(propylenimine) (PPI) are delivering conjugated nucleic acids efficiently. Additionally, its comparatively low toxicity, biodegradability, and biocompatibility makes PAMAM preferable over PEI [ 27 ]. An even safer possibility are neutral Poly(lactide-co-glycolide) (PLGA) particles, which show no toxicity, but also a lower miR binding capacity.…”

Section: Delivery Of Mir Therapeuticsmentioning

confidence: 99%

“…Inorganic nanoparticles have also been employed for miR transport in several studies. They are non-toxic, non-immunogenic, and are highly stable in vivo, but on the downside show non-specific binding affinities to functional groups in biological systems and colloidal stability [ 27 ]. The most extensively used inorganic vesicles for miR therapeutics are silica or gold nanoparticles (AuNPs).…”

Section: Delivery Of Mir Therapeuticsmentioning

confidence: 99%

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Therapeutic Targeting of MicroRNAs in the Tumor Microenvironment

Raue

Frank

Syed

et al. 2021

IJMS

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The tumor-microenvironment (TME) is an amalgamation of various factors derived from malignant cells and infiltrating host cells, including cells of the immune system. One of the important factors of the TME is microRNAs (miRs) that regulate target gene expression at a post transcriptional level. MiRs have been found to be dysregulated in tumor as well as in stromal cells and they emerged as important regulators of tumorigenesis. In fact, miRs regulate almost all hallmarks of cancer, thus making them attractive tools and targets for novel anti-tumoral treatment strategies. Tumor to stroma cell cross-propagation of miRs to regulate protumoral functions has been a salient feature of the TME. MiRs can either act as tumor suppressors or oncogenes (oncomiRs) and both miR mimics as well as miR inhibitors (antimiRs) have been used in preclinical trials to alter cancer and stromal cell phenotypes. Owing to their cascading ability to regulate upstream target genes and their chemical nature, which allows specific pharmacological targeting, miRs are attractive targets for anti-tumor therapy. In this review, we cover a recent update on our understanding of dysregulated miRs in the TME and provide an overview of how these miRs are involved in current cancer-therapeutic approaches from bench to bedside.

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Section: Mechanisms Of Mir Dysregulation In the Tmementioning

confidence: 99%

Section: Delivery Of Mir Therapeuticsmentioning

confidence: 99%

Section: Delivery Of Mir Therapeuticsmentioning

confidence: 99%

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Therapeutic Targeting of MicroRNAs in the Tumor Microenvironment

Raue

Frank

Syed

et al. 2021

IJMS

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“…MicroRNA is emerging as a next generation cancer treatment [41][42][43][44]. Studies showed that miR-1291 had anti-tumor effects in multiple cancers including renal cancer, esophagus cancer, pancreatic cancer, and prostate cancer [31][32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor effect of miR-1291 in colorectal cancer

Wang

Hirose

Yokoyama

et al. 2020

Preprint

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Background: MiR-1291 has an anti-tumor effect in carcinoma of kidney, esophagus, pancreas, and prostate. However, it’s role in colorectal cancer (CRC) has not been elucidated.Methods: In this study, we explored the effect of miR-1291 in CRC cells (HCT116, DLD-1, and HT29) in vitro, and performed a tumor growth inhibitory assay in a mouse therapeutic model using DLD-1 cells. Flow cytometric analysis and Western blotting were performed to examine a role of miR-1291 in cell cycle regulation. We performed luciferase reporter assay to verify the interaction between DCLK1 and miR-1291 in HCT116 cells. Cancer stemness was evaluated by identifying the expression of BMI1 and CD133, as well as performing sphere formation assay. Results: We found that miR-1291 significantly suppressed the proliferation, invasion, cell mobility, and colony formation capability of CRC cell lines. MiR-1291 caused altered expression of the cell cycle-regulatory proteins, representatively CDK inhibitors p21WAF1/CIP1 and p27KIP1 or CDK4. Moreover, intravenous administration of miR-1291 loaded on the super carbonate apatite delivery system significantly inhibited a tumor growth in the DLD-1 xenograft mouse model. A luciferase reporter assay showed that miR-1291 directly bound the 3’ UTR sequence of DCLK1 and suppressed its expression at both the mRNA and protein levels in HCT116 expressing the DCLK1 protein. In addition, miR-1291 suppressed cancer stem cell (CSC) markers BMI1 and CD133 as well as sphere formation ability in HCT116 cells. Conclusions: Taken together, these findings indicate that miR-1291 has an anti-tumor effect by modulating multiple functions, including cell cycle, invasiveness, and cancer stemness. Our data suggest that miR-1291 could be a promising nucleic acid medicine against CRC.

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“…In this sense, many diseases have been associated with changes in the expression level of miRNAs, including systemic rheumatic diseases, nervous system disorders, sepsis, cardiovascular disease and different type of cancers such as breast, ovarian, cervical forms (Ceribelli et al, 2011;Abd-Aziz et al, 2020;Ali Syeda et al, 2020;Condrat et al, 2020). In addition, several investigations have recently demonstrated changes in circulating miRNAs in response to different infectious diseases, increasing the possibility for a new diagnostic tool (Acuña et al, 2020;Tribolet et al, 2020), even before the pathogen could be directly distinguished and prior to the onset of seroconversion (Stewart et al, 2013;Biswas et al, 2019).…”

Section: Mirnas and Diseasesmentioning

confidence: 99%