Involvement of CD40 Targeting miR-224 and miR-486 on the Progression of Pancreatic Ductal Adenocarcinomas

Mees, Soeren Torge; Mardin, Wolf Arif; Sielker, Sonja; Willscher, Edith; Senninger, N.; Schleicher, Christina; Colombo-Benkmann, Mario; Haier, Joerg

doi:10.1245/s10434-009-0531-4

Cited by 120 publications

(102 citation statements)

References 44 publications

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“…miR-224 is reported to be overexpressed in various types of cancer (15)(16)(17)(18)(19)(20), and it plays critical roles in malignant phenotypes. Consistent with these previous observations, miR-224 was found to be upregulated in HepG2 cells in our study.…”

Section: Discussionmentioning

confidence: 99%

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miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

Ma¹,

Tao²,

Gao³

et al. 2012

Oncology Letters

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Abstract. microRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate gene expression. Increasing evidence has shown that the deregulation of miRNAs is linked to cancer. The overexpression of miR-224 has been reported in several human cancers. The aim of the present study was to investigate the function of miR-224 in the pathogenetic process of hepatocellular carcinoma (HCC), and the precise mechanism underlying its function. Both gain-of-function and loss-of function assays were conducted through transfection with miR-224 mimics and miR-224 inhibitors in the HepG2 liver carcinoma cell line. The data revealed that miR-224 exerts a significant role in promoting cell proliferation, migration and invasion. Western blot analysis showed that the phosphorylation levels of AKT positively correlated with endogenous levels of miR-224. In addition, results from a dual luciferase reporter assay showed that the expression of the serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A β isoform (PPP2R1B) is inhibited by miR-224; thus, it appears that PPP2R1B is a candidate target of miR-224 in HCC. These data suggest that miR-224 plays a significant role in HCC, possibly through the activation of the AKT signaling pathway by targeting PPP2R1B.

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Section: Discussionmentioning

confidence: 99%

“…The abnormal expression of miR-224 has been reported in several human cancers (15)(16)(17)(18)(19). Wang et al found that miR-224 is upregulated in HCC patients and HCC cell lines (20), and promotes HCC cell apoptosis by targeting the transcript expression levels of apoptosis inhibitor 5 (API-5).…”

Section: Introductionmentioning

confidence: 99%

miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

Ma¹,

Tao²,

Gao³

et al. 2012

Oncology Letters

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show abstract

“…It should be also noted that these miRNAs have other predicted and experimentally validated targets. For example, miR-224 is up-regulated in highly invasion pancreatic ductal adenocarcinoma, and it is correlated with the down-regulation of CD40, which it is predicted to target (Mees et al, 2009). MiR-224 is also predicted to target apoptosis inhibitor-5 in hepatocellular carcinoma; it is found to be significantly up-regulated in hepatocellular carcinoma and as a result inhibits apoptosis and induces tumourigenesis .…”

Section: Discussionmentioning

confidence: 99%

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

et al. 2010

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BACKGROUND: Kallikrein-related peptidases (KLKs) are a family of serine proteases that have been shown to be dysregulated in several malignancies including ovarian cancer. The control of kallikrein genes and their physiological function in cancer is not well understood. We hypothesized that microRNAs (miRNAs) represent a novel mechanism for post-transcriptional control of KLK expression in cancer. METHODS: We first analysed miRNA expression in ovarian cancer in silico. A total of 98 miRNAs were reported to have altered expression in ovarian cancer. Three of these miRNAs were predicted to target KLK10. We experimentally verified the predicted miR -KLK10 interaction using two independent techniques, a luciferase assay with a construct containing the KLK10 3 0 untranslated region (UTR), pMIR -KLK10, and measuring KLK10 protein levels after transfection with miRNA. RESULTS: When we co-transfected cells with pMIR -KLK10 and either let-7f, miR-224, or mR-516a, we saw decreased luciferase signal, suggesting that these miRNAs can target KLK10. We then examined the effect of these three miRNAs on KLK10 protein expression and cell growth. Transfection of all miRNAs, let-7f, miR-224, and miR-516a led to a decrease in protein expression and cellular growth. This effect was shown to be dose dependent. The KLK10 protein levels were partially restored by co-transfecting let-7f and its inhibitor. In addition, there was a slight decrease in KLK10 mRNA expression after transfection with let-7f. CONCLUSIONS: Our results confirm that KLKs can be targeted by more than one miRNA. Increased expression of certain miRNAs in ovarian cancer can lead to decreased KLK protein expression and subsequently have a negative effect on cell proliferation. This dose-dependent effect suggests that a 'tweaking' or 'fine-tuning' mechanism exists in which the expression of one KLK can be controlled by multiple miRNAs. These data together suggest that miRNA may be used as potential therapeutic options and further studies are required.

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“…miR-224 has been revealed to be upregulated in various types of tumor when functioning as an oncogene (79)(80)(81). Nevertheless, a previous study identified that miR-224 was downregulated in mucinous cystic neoplasms (MCNs) of the pancreas (81).…”

Section: Gastric Cancermentioning

confidence: 99%

Crosstalk between the Notch signaling pathway and non‑coding RNAs in gastrointestinal cancers (Review)

2017

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Abstract. The Notch signaling pathway is one of the main signaling pathways that mediates direct contact between cells, and is essential for normal development. It regulates various cellular processes, including cell proliferation, apoptosis, migration, invasion, angiogenesis and metastasis. It additionally serves an important function in tumor progression. Non-coding RNAs mainly include small microRNAs, long non-coding RNAs and circular RNAs. At present, a large body of literature supports the biological significance of non-coding RNAs in tumor progression. It is also becoming increasingly evident that cross-talk exists between Notch signaling and non-coding RNAs. The present review summarizes the current knowledge of Notch-mediated gastrointestinal cancer cell processes, and the effect of the crosstalk between the three major types of non-coding RNAs and the Notch signaling pathway on the fate of gastrointestinal cancer cells.

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Involvement of CD40 Targeting miR-224 and miR-486 on the Progression of Pancreatic Ductal Adenocarcinomas

Cited by 120 publications

References 44 publications

miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

Crosstalk between the Notch signaling pathway and non‑coding RNAs in gastrointestinal cancers (Review)

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