MicroRNA: Promising Roles in Cancer Therapy

Hashemi, Atieh; Gorji-Bahri, Gilar

doi:10.2174/1389201021666200420101613

Cited by 23 publications

(15 citation statements)

References 145 publications

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“…In recent years, biological therapy has been widely used for cancer treatment (5,6). MicroRNAs (miRNAs) are endogenous, noncoding RNAs, with approximately 22 nucleotides.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-377-3p targeting MMP-16 inhibits ovarian cancer cell growth, invasion, and interstitial transition

Wang

Wan

2021

Ann Transl Med

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Background: To evaluate role of microRNA (miRNA)-377-3p on the remission of ovarian cancer (OC) cell proliferation, invasion, and interstitial transition in vivo and vitro. Methods: SKOV3 cells were used as the object of in vitro research and four-week-old immunodeficient BABL/c female nude mice were used to form the xenograft model. Cell models were constructed by transfecting NC mimics, miR-377 mimic, plasmid cloning DNA (pcDNA), pc-matrix metalloproteinase (MMP)-16, or co-transfecting miR-377 mimic and pc-MMP-16. TargetScan software was used to predict the targeting relationship between miRNA-377-3p and MMP-16 in OC cells. The combination of miRNA-377-3p and MMP-16 was detected by dual luciferase report experiment. miRNA expression levels of miRNA-377-3p and MMP-16 in each transfection group cells were detected by reverse transcription-polymerase chain reaction (RT-PCR). The proliferation of SKOV3 cells were assessed by 5-ethynyl-2'-deoxyuridine (EdU) staining and microtubule formation, while the invasion ability of SKOV3 cells was detected by Transwell assay. Protein expression levels of MMP-16, survivin, Ki67, vascular endothelial growth factor (VEGF), E-cadherin, and N-cadherin were detected by Western blot (WB), and the positive cells of Ki67 and VEGF were detected by immunohistochemistry (IHC). Results: MMP-16 overexpression markedly increased the EDU-positive cell percentage, upregulated survivin and Ki67 levels, increased the number of invasive cells per field, and enhanced VEGF and N-cadherin expression. Importantly, co-transfection of miRNA-377-3p and MMP-16 reversed these abnormal phenomena. Xenotransplantation mouse models were formed by injecting SKOV-3 cells subcutaneously.Tumor size, tumor volume, and tumor weight were all reduced in the miR-377-3p mimic-transfected group.The results of IHC indicated that Ki67 and VEGF expression were decreased in the miR-377-3p mimictransfected group.Conclusions: These findings indicate that miR-377-3p could be a promising therapeutic agent for OC cell growth, invasion, and interstitial transition with MMP-16 being its likely target.

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“…In recent years, biological therapy has been widely used for cancer treatment (5,6). MicroRNAs (miRNAs) are endogenous, noncoding RNAs, with approximately 22 nucleotides.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-377-3p targeting MMP-16 inhibits ovarian cancer cell growth, invasion, and interstitial transition

Wang

Wan

2021

Ann Transl Med

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“…This indicates the potential of miRs to modulate several pathways and cellular networks (14). In oncology, miRs can affect the whole cascade of oncogenic events from tumor initiation, tumor progression and metastasis, as well as angiogenesis, to interactions with the immune system and the tumor microenvironment (15)(16)(17). Several miRs may act as oncogenes or tumor suppressors in a context-dependent way, depending on the cell-type in which they are expressed (18).…”

Section: Mirs In Cancermentioning

confidence: 99%

Gastric Cancer: Identification of microRNAs Inhibiting Druggable Targets and Mediating Efficacy in PreclinicalIn VivoModels

Weidle

Birzele

Brinkmann

et al. 2021

Cancer Genomics Proteomics

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In addition to chemotherapy, targeted therapies have been approved for treatment of locally advanced and metastatic gastric cancer. The therapeutic benefit is significant but more durable responses and improvement of survival should be achieved. Therefore, the identification of new targets and new approaches for clinical treatment are of paramount importance. In this review, we searched the literature for down-regulated microRNAs which interfere with druggable targets and exhibit efficacy in preclinical in vivo efficacy models. As druggable targets, we selected transmembrane receptors, secreted factors and enzymes. We identified 38 microRNAs corresponding to the criteria as outlined. A total of 13 miRs target transmembrane receptors, nine inhibit secreted proteins and 16 attenuate enzymes. These microRNAs are targets for reconstitution therapy of gastric cancer. Further target validation experiments are mandatory for all of the identified microRNAs.Gastric cancer (GC) is the third-leading cause of cancer worldwide and is the fourth most common cancer with an annual death toll of 700 000 worldwide (1). From a molecular point of view the following subtypes have been characterized: Epstein-Barr virus, microsatellite instability, genomically stable and chromosomal instability subtypes, all correlate with differential prognosis (2). Of all GCs, 90% are adenocarcinomas which arise from the glandular epithelium (2). The only curative treatment is surgery. Neo-adjuvant and adjuvant treatment are integrated with chemotherapy and radiation, nevertheless the 5-year survival rate for patients with locally advanced disease is less than 30% and in the metastatic setting, the median survival is in the range of 1 year (3-5). Preferential organs of metastasis are the liver (48%), peritoneum (32%), lung (15%) and bone (12%) (6). New treatment modalities have been introduced, such as trastuzumab in the subclass of patients with human epidermal growth factor receptor 2 (HER2)-positive tumors, and ramucirumab as second-line treatment or in combination with paclitaxel (3-5). More recently, immune-checkpoint inhibitory monoclonal antibodies (mAbs) against programmed cell death protein 1 (PD1), such as nivolumab and pembrolizumab, have been approved for patients with heavily pre-treated GC (3-6). Promising clinical studies are ongoing in claudin 18.2-positive GCs and in those with fibroblast growth factor receptor 2 (FGFR2) amplification (3-6). Nevertheless, there is an urgent need to identify new targets and treatment modalities which lead to durable responses and improved survival. Many of the recently identified targets, e.g., those involved in epigenetic modification or tumor suppressors, are undruggable or difficult to interfere with (7-9). In this review, we focus on microRNAs (miRs) which are down-regulated in GC and interfere with controllable targets (transmembrane receptors, secreted factors and enzymes) with demonstrated efficacy in GC-related preclinical in vivo models. The identified targets need to be validated for treatme...

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“…The introduction of exogenous nucleic acids in the form of plasmid vectors, antisense oligonucleotides or mRNA, to name a few, enables complete elimination of pathological cells (for example, using ‘suicide genes’) and/or limitation of their proliferation (by silencing expression of oncogenes or restoring function of key suppressors) [ 1 ]. Most recently, a broad range of non-coding RNA molecules have been shown to fine-tune not only gene expression but also genome remodeling, thus becoming new tools to modulate disease-related physiological processes [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Polyethyleneimine-Based Lipopolyplexes as Carriers in Anticancer Gene Therapies

Jerzykiewicz

Czogalla

2021

Materials

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Recent years have witnessed rapidly growing interest in application of gene therapies for cancer treatment. However, this strategy requires nucleic acid carriers that are both effective and safe. In this context, non-viral vectors have advantages over their viral counterparts. In particular, lipopolyplexes—nanocomplexes consisting of nucleic acids condensed with polyvalent molecules and enclosed in lipid vesicles—currently offer great promise. In this article, we briefly review the major aspects of developing such non-viral vectors based on polyethyleneimine and outline their properties in light of anticancer therapeutic strategies. Finally, examples of current in vivo studies involving such lipopolyplexes and possibilities for their future development are presented.

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MicroRNA: Promising Roles in Cancer Therapy

Cited by 23 publications

References 145 publications

MicroRNA-377-3p targeting MMP-16 inhibits ovarian cancer cell growth, invasion, and interstitial transition

MicroRNA-377-3p targeting MMP-16 inhibits ovarian cancer cell growth, invasion, and interstitial transition

Gastric Cancer: Identification of microRNAs Inhibiting Druggable Targets and Mediating Efficacy in PreclinicalIn VivoModels

Polyethyleneimine-Based Lipopolyplexes as Carriers in Anticancer Gene Therapies

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