Both pro- and anti-oncogenic roles of miR-221 and miR-222 microRNAs are reported in several types of human cancers. A previous study suggested their oncogenic role in invasiveness in lung cancer, albeit only one cell line (H460) was used. To further evaluate involvement of miR-221 and miR-222 in lung cancer, we investigated the effects of miR-221 and miR-222 overexpression on six lung cancer ce...

The activity of a peptide nucleic acid (PNA) targeting cancer-associated microRNA-221 is described. PNAs against miR-221 were designed in order to bind very efficiently to the target RNA strand and to undergo efficient uptake in the cells. A polyarginine-PNA conjugate targeted against miR-221 (Rpep-PNA-a221) showed both very high affinity for RNA ...

MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that have emerged as key posttranscriptional regulators in a wide variety of organisms. Because any one miRNA can potentially regulate expression of a distinct set of genes, differential miRNA expression can shape the repertoire of proteins that are actually expressed during development and differentiation or disease. Here, we...

BACKGROUND Previous studies have examined the relation between postmenopausal estrogen replacement therapy (ERT) and the risk of Alzheimer disease (AD). The findings have been inconsistent, since some studies have been interpreted as showing a protective effect while others have reported no effect. OBJECTIVE To determine whether exposure to ERT is associated with a reduced risk of AD. DESIG...

MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed 'small RNA zipper'. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-...

miR-221 and miR-222 (miR-221/222) are frequently up-regulated in human epithelial cancers. However, the mechanism of miR-221/222 action involved in carcinogenesis has not been extensively studied. Here, we found that reduction of miR-221/222 inhibited cell proliferation and induced mitochondrial-mediated apoptosis in human epithelial cancer cells (A549 lung cancer and MCF-7 breast cancer cells)...

BACKGROUND Although Helicobacter pylori infection is necessary for development of gastric adenocarcinoma (GAC), the underlying mechanism remains poorly defined. This study aimed to explore how miR-221 and miR-222 are dysregulated after H. pylori infection and how these 2 miRNAs are involved in pathological development of gastric cancer. MATERIAL AND METHODS qRT-PCR analysis was performed to q...

Locked nucleic acid (LNA) oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics a...

Patients with advanced hepatocellular carcinoma (HCC) face a dismal prognosis because of a lack of any effective therapies. To address this situation, we conducted a preclinical investigation of the therapeutic efficacy of oligonucleotides directed against the oncogenic microRNA miR-221, which has been implicated in HCC. Of 9 chemistries evaluated, we determined that a 2'-O-methyl phosphorothio...

Despite recent therapeutic advances that have doubled the median survival time of patients with multiple myeloma, intratumor genetic heterogeneity contributes to disease progression and emergence of drug resistance. miRNAs are noncoding small RNAs that play important roles in the regulation of gene expression and have been implicated in cancer progression and drug resistance. We investigated th...