miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer

Zhao, Dongfang; Sui, Yanxia; Zheng, Xiaoqiang

doi:10.3892/or.2015.4450

Cited by 74 publications

(69 citation statements)

References 42 publications

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“…In addition to siRNA, miRNAs are also potential vectors for HER2 silencing. For example, miR-331-3p has recently been shown to reduce proliferation and increase apoptosis in colorectal cancer cells via HER2 silencing 36 . Small RNA loading into EVs via sonication enables increased options for delivery of both siRNA and miRNA against HER2 and other oncogenes, and thus may be useful in a variety of cancer therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

Oncogene Knockdown via Active Loading of Small RNAs into Extracellular Vesicles by Sonication

et al. 2016

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Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as promising drug delivery vehicles for small RNAs (siRNA and miRNA) due to their natural role in intercellular RNA transport. However, the application of EVs for therapeutic RNA delivery may be limited by loading approaches that can induce cargo aggregation or degradation. Here, we report the use of sonication as a means to actively load functional small RNAs into EVs. Conditions under which EVs could be loaded with small RNAs with minimal detectable aggregation were identified, and EVs loaded with therapeutic siRNA via sonication were observed to be taken up by recipient cells and capable of target mRNA knockdown leading to reduced protein expression. This system was ultimately applied to reduce expression of HER2, an oncogenic receptor tyrosine kinase that critically mediates breast cancer development and progression, and could be extended to other therapeutic targets. These results define important parameters informing the application of sonication as a small RNA loading method for EVs and demonstrate the potential utility of this approach for versatile cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Oncogene Knockdown via Active Loading of Small RNAs into Extracellular Vesicles by Sonication

et al. 2016

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“…PGE2 is a known pro-inflammatory lipid mediator and promotes tumor progression via several mechanisms such as regulation of cell proliferation, induction of tumor cells to secrete growth factors, and immunomodulation for the escape of tumor cells from effective immunosurveillance [165]. Zhao et al [166] examined different human colon cancer cell-lines, e.g. HCT116, LoVo, HT-29, SW480, DLD-1 and Caco-2; and found that HER2 was overexpressed in these cells.…”

Section: Tumors Of Other Organs and Her2 Expression Malignant Diseasementioning

confidence: 99%

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Ray

2017

Hormone Molecular Biology and Clinical Investigation

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Abstract:Obesity is associated with the risk of several health disorders including certain cancers. Among obesity-related cancers, postmenopausal breast carcinoma is a well-studied one. Apart from an increase in certain types of lipids in obesity, excess adipose tissue releases many hormone-like cytokines/adipokines, which are usually pro-inflammatory in nature. Leptin is one of such adipokines and significantly linked with the intracellular signaling pathways of other growth factors such as insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2). In general, HER2 is overexpressed in roughly 30% of breast carcinomas; its presence indicates aggressive tumor behavior. Conversely, HER2 has certain effects in normal conditions such as differentiation of preadipocytes, cardiovascular health and vitamin D metabolism. HER2 has no known endogenous ligand, but it may form dimers with other three members of the epidermal growth factor receptor (EGFR) family and can activate downstream signaling pathways. Furthermore, HER2 is intimately connected with several enzymes, e.g. fatty acid synthase (FASN), phosphatidylinositol 3-kinase (PI3K), AKT and mechanistic target of rapamycin (mTOR), all of which play significant regulatory roles in lipogenic pathways or lipid metabolism. In obesity-related carcinogenesis, characteristics like insulin resistance and elevated IGF-1 are commonly observed. Both IGF-1 and leptin can modulate EGFR and HER2 signaling pathways. Although clinical studies have shown mixed results, the behavior of HER2+ tumor cells including HER2 levels can be altered by several factors such as obesity, leptin and fatty acids. A precise knowledge is useful in new therapeutic approaches against HER+ tumors.

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“…1 MiRNAs not only can act as oncogenes and tumor suppressors directly 4,5 but also play a role in COAD by regulating the expression of their targeting genes. 6,7 Hence, identifying the key miRNAs in early-stage COAD is also crucial. With advanced high-throughput technology, both RNA-sequencing and microarray analysis can be used to identify differentially expressed genes (DEGs) and miRNAs (DEmiRNAs).…”

Section: Introductionmentioning

confidence: 99%

Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing

Liu

et al. 2017

Tumour Biol.

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Colon adenocarcinoma is the third leading cause of cancer-related deaths across the world, developing novel and non-invasive diagnostic and prognostic biomarkers for the early-stage colon adenocarcinoma at molecular level is essential. In our study, RNA-sequencing was performed to identify the differentially expressed genes and miRNAs (DEmiRNAs) in early-stage colon adenocarcinoma compared to tissues of precancerous lesions, colonic intraepithelial neoplasia. The DEmiRNA-target interaction network was constructed and functional annotation of targets of DEmiRNAs was performed. The Cancer Genome Atlas was used to verify the expression of selected differentially expressed genes. The receiver operating characteristic analyses of selected differentially expressed genes was performed. In total, 865 differentially expressed genes, 26 DEmiRNAs, and 329 DEmiRNA-target pairs were obtained. Based on the early-stage colon adenocarcinoma network, miR-548c-5p, miR-548i, and miR-548am-5p were the top three DEmiRNAs that covered most differentially expressed genes. NTRK2, DTNA, and BTG2 were the top three differentially expressed genes regulated by most DEmiRNAs. Cancer and colorectal cancer pathways were two significantly enriched pathways in early-stage colon adenocarcinoma. The common differentially expressed genes in both the pathways were AXIN2, Smad2, Smad4, PIK3R1, and BCL2. The expression levels of eight differentially expressed genes (NTRK2, DTNA, BTG2, COL11A1, Smad2, Smad4, PIK3R1, and BCL2) in The Cancer Genome Atlas database were compatible with our RNA-sequencing. All these eight differentially expressed genes and AXIN2 had the potential diagnosis value for Colon adenocarcinoma. In conclusion, a total of ten differentially expressed genes (NTRK2, DTNA, BTG2, COLCA1, COL11A1, AXIN2, Smad2, Smad4, PIK3R1, and BCL2) and four DEmiRNAs (miR-548c-5p, miR-548i, mir-424-5p, and miR-548am-5p) may be involved in the pathogenesis of early-stage colon adenocarcinoma which may make a contribution for developing new diagnostic and therapeutic strategies for early-stage colon adenocarcinoma.

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miR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer

Cited by 74 publications

References 42 publications

Oncogene Knockdown via Active Loading of Small RNAs into Extracellular Vesicles by Sonication

Oncogene Knockdown via Active Loading of Small RNAs into Extracellular Vesicles by Sonication

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing

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