An insight of microRNAs performance in carcinogenesis and tumorigenesis; an overview of cancer therapy

Babaei, Kosar; Shams, Shima; Keymoradzadeh, Arman; Vahidi, Sogand; Hamami, Parisa; Khaksar, Roya; Norollahi, Seyedeh Elham; Samadani, Ali Akbar

doi:10.1016/j.lfs.2019.117077

Cited by 48 publications

(38 citation statements)

References 96 publications

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“…MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression by repressing the stability of conventional mRNAs and/or inhibiting their translation into proteins. [ 3 ] Recent studies have demonstrated that miRNAs are differentially expressed in lung, nasopharyngeal, gastric and breast cancers, and may function as either oncogenes or tumor suppressors by controlling the expression of their target genes. [ 4 – 6 ] The overexpression of several miRNAs, such as miR-145 and miR-224–5p, has been demonstrated an inhibitory role in migration, proliferation, and invasion of UM cells.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-145 suppresses uveal melanoma angiogenesis and growth by targeting neuroblastoma RAS viral oncogene homolog and vascular endothelial growth factor

Yang

Wang

et al. 2020

Chinese Medical Journal

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Background Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. It has been demonstrated that microRNA-145 (miR-145) is correlated with the progression of various cancers by regulating the expression of multiple target genes, especially a number of genes that regulate angiogenesis and proliferation. However, the underlying mechanisms of miR-145 in tumor angiogenesis of UM are still not well illustrated. Thus, we aimed to explore the potential target genes or pathways regulated by miR-145 in UM and the effect of miR-145 on invasion and angiogenesis. Methods Totally, 24 choroid samples were collected in our study, including 12 UM samples and 12 normal uveal tissues. The expression of neuroblastoma RAS viral oncogene homolog (N-RAS), phosphorylated protein kinase B (p-AKT), and vascular endothelial growth factor (VEGF) in UM tissues and normal uveal tissues was analyzed using Western blotting analysis. Lentivirus expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of miR-145. Transwell and endothelial cell tube formation assay were used to measure the effects of miR-145 on the invasion and angiogenesis of UM in vitro . The downstream target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase assay. BALB/c nude mice models were established to investigate the mechanisms of miR-145 on tumor growth and angiogenesis in vivo . Group data comparisons were performed using analysis of Student's t test. A two-tailed P < 0.05 was considered as statistically significant. Results The results of Western blotting analysis indicated that the expressions of N-RAS (1.10 ± 0.35 vs. 0.41 ± 0.36, t = 3.997, P = 0.012), p-AKT (1.16 ± 0.22 vs. 0.57 ± 0.03, t = 7.05, P = 0.001), and VEGF (0.97 ± 0.32 vs. 0.45 ± 0.21, t = 3.314, P = 0.008) in UM tumor tissues were significantly higher than those in normal uveal tissue. Luciferase assay demonstrated N-RAS and VEGF as downstream targets of miR-145. Moreover, tube formation assay revealed that miR-145-transfected human microvascular endothelial cell line formed shorter tube length (36.10 ± 1.51 mm vs. 42.91 ± 0.94 mm, t = 6.603, P = 0.003) and less branch points (350.00 ± 19.97 vs. 406.67 ± 17.62, t = 3.685, P = 0.021) as compared with controls. In addition, the numbers of invaded MUM-2B and OCM-1 cells with miR-145 overexpression were significantly lower than the controls (35.7 ± 3.3 ...

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Section: Introductionmentioning

confidence: 99%

MicroRNA-145 suppresses uveal melanoma angiogenesis and growth by targeting neuroblastoma RAS viral oncogene homolog and vascular endothelial growth factor

Yang

Wang

et al. 2020

Chinese Medical Journal

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“…miRNAs are small, endogenous single-stranded 21–23 nucleotide non-coding RNAs that serve as protooncogenes or tumor suppressor genes, and are abnormally expressed in a variety of tumors. Increasing bioinformatics evidence and subsequent functional assays have revealed that miRNAs serve key roles in numerous biological processes, including tumor occurrence, development and metastasis, in several types of cancer ( 21 ). miRNAs can bind to the 3′-UTR of target gene mRNAs and induce their post-transcriptional repression ( 22 – 24 ).…”

Section: Discussionmentioning

confidence: 99%

Halofuginone inhibits tumorigenic progression of 5‑FU‑resistant human colorectal cancer HCT‑15/FU cells by targeting miR‑132‑3p <em>in vitro</em>

Wang¹,

Zhu²,

Yan

et al. 2020

Oncol Lett

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5-Fluorouracil (5-FU)-based chemotherapy is the first-line option for patients with advanced colorectal cancer (CRC). However, the development of chemoresistance is the primary cause of treatment failure. Halofuginone (HF), a small molecule alkaloid derived from febrifugine, has been demonstrated to exert strong anti-proliferative effects. However, to the best of our knowledge, whether HF inhibits the progression of 5-FU-resistant human CRC HCT-15/FU cells, and the underlying mechanisms, remain unknown. In the present study, the effects of HF on HCT-15/FU cells were assessed in vitro . The results revealed that HF inhibited HCT-15/FU cell viability as demonstrated by the MTT and colony formation assays. Following treatment of HCT-15/FU cells with HF, the migratory and invasive capacities of the cells were significantly decreased. MicroRNA (miRNA/miR)-sequencing data, subsequent miRNA trend analysis and reverse transcription-quantitative PCR all demonstrated that miR-132-3p expression was increased following treatment with HF in a dose-dependent manner. Western blot analysis indicated that following treatment with HF, the expression levels of proteins associated with proliferation, invasion and metastasis in cells were markedly downregulated. These results suggested that HF inhibited the proliferation, invasion and migration of HCT-15/FU cells by upregulating the expression levels of miR-132-3p. Therefore, miR-132-3p may serve as a molecular marker, which may be used to predict CRC resistance to 5-FU, and HF may serve as a novel clinical treatment for 5-FU-resistant CRC.

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“…Several studies proposed the reposition of miRNAs envisaging cancer therapy, including for example, by adding the tumor suppressor miRNA Let-7c for prostate cancer treatment, by silencing the oncomirs miR-21 in breast cancer, or by over-expressing miR-143 in colon cancer to overcome oxaliplatin resistance [13,104,105]. The systemic administration of free miRNAs for therapy has been challenged by single stranded or double stranded miRNA degradation in the circulatory system or in the endosome, potential off-target effects, miRNA-mediated toxicity and poor delivery [106][107][108]. The knowledge of the miRNAs metabolic modulation in targeted and non-targeted cells is preponderant to avoid off-target effect that occurs due to partial complementarity with non-targeted transcripts, or by leading to undesired effects by regulation of metabolic processes in non-targeted cells [107].…”

Section: Microrna Targeted Therapymentioning

confidence: 99%

Gene Therapy in Cancer Treatment: Why Go Nano?

et al. 2020

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The proposal of gene therapy to tackle cancer development has been instrumental for the development of novel approaches and strategies to fight this disease, but the efficacy of the proposed strategies has still fallen short of delivering the full potential of gene therapy in the clinic. Despite the plethora of gene modulation approaches, e.g., gene silencing, antisense therapy, RNA interference, gene and genome editing, finding a way to efficiently deliver these effectors to the desired cell and tissue has been a challenge. Nanomedicine has put forward several innovative platforms to overcome this obstacle. Most of these platforms rely on the application of nanoscale structures, with particular focus on nanoparticles. Herein, we review the current trends on the use of nanoparticles designed for cancer gene therapy, including inorganic, organic, or biological (e.g., exosomes) variants, in clinical development and their progress towards clinical applications.

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An insight of microRNAs performance in carcinogenesis and tumorigenesis; an overview of cancer therapy

Cited by 48 publications

References 96 publications

MicroRNA-145 suppresses uveal melanoma angiogenesis and growth by targeting neuroblastoma RAS viral oncogene homolog and vascular endothelial growth factor

MicroRNA-145 suppresses uveal melanoma angiogenesis and growth by targeting neuroblastoma RAS viral oncogene homolog and vascular endothelial growth factor

Halofuginone inhibits tumorigenic progression of 5‑FU‑resistant human colorectal cancer HCT‑15/FU cells by targeting miR‑132‑3p <em>in vitro</em>

Gene Therapy in Cancer Treatment: Why Go Nano?

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An insight of microRNAs performance in carcinogenesis and tumorigenesis; an overview of cancer therapy

Cited by 48 publications

References 96 publications

MicroRNA-145 suppresses uveal melanoma angiogenesis and growth by targeting neuroblastoma RAS viral oncogene homolog and vascular endothelial growth factor

MicroRNA-145 suppresses uveal melanoma angiogenesis and growth by targeting neuroblastoma RAS viral oncogene homolog and vascular endothelial growth factor

Halofuginone inhibits tumorigenic progression of 5‑FU‑resistant human colorectal cancer HCT‑15/FU cells by targeting miR‑132‑3p <em>in&nbsp;vitro</em>

Gene Therapy in Cancer Treatment: Why Go Nano?

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Halofuginone inhibits tumorigenic progression of 5‑FU‑resistant human colorectal cancer HCT‑15/FU cells by targeting miR‑132‑3p <em>in vitro</em>