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Molecular Therapy. Nucleic Acids

Yuhong Sun, Yan Hou, Nan Lv, Qian Liu, Nan Lin, Shuyu Zhao, Xiaodan Chu, Xuan Chen, Guobin Cheng, Peiling Li
Long noncoding RNAs (lncRNAs) have increasingly been shown to be important biological regulators involved in numerous diseases. Further, increasing evidence demonstrates that circulating lncRNAs can be used as diagnostic biomarkers. Therefore, the purpose of this study was to evaluate the potential for circulating lncRNAs as novel biomarkers for the diagnosis of preeclampsia. In the present study, we measured the expression of five lncRNAs known to be relevant to the uterus in whole blood samples from 48 preeclampsia patients and 24 non-preeclampsia healthy subjects using qRT-PCR...
February 1, 2019: Molecular Therapy. Nucleic Acids
Raygene Martier, Jolanda M Liefhebber, Jana Miniarikova, Tom van der Zon, Jolanda Snapper, Iris Kolder, Harald Petry, Sander J van Deventer, Melvin M Evers, Pavlina Konstantinova
The most common pathogenic mutation in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an intronic GGGGCC (G4 C2 ) repeat in the chromosome 9 open reading frame 72 (C9orf72) gene. Cellular toxicity due to RNA foci and dipeptide repeat (DPR) proteins produced by the sense and antisense repeat-containing transcripts is thought to underlie the pathogenesis of both diseases. RNA sequencing (RNA-seq) data of C9orf72-ALS patients and controls were analyzed to better understand the sequence conservation of C9orf72 in patients...
January 30, 2019: Molecular Therapy. Nucleic Acids
Jia Ma, Tong Cao, Yue Cui, Fan Zhang, Ying Shi, Jun Xia, Z Peter Wang
Emerging evidence has demonstrated that miR-223 is critically involved in the progression of pancreatic cancer (PC); however, the underlying mechanisms are not fully elucidated. In the present study, we explored the molecular basis of miR-223-mediated tumor progression in PC. We performed numerous approaches including MTT, FACS, transfection, RT-PCR, western blotting, Transwell, and animal studies to determine the physiological role of miR-223 in PC cells. We found that sister chromatid cohesion protein PDS5 homolog B (PDS5B) is a direct target of miR-223 in PC...
January 29, 2019: Molecular Therapy. Nucleic Acids
Shouta Miyatake, Yoshitaka Mizobe, Maria K Tsoumpra, Kenji Rowel Q Lim, Yuko Hara, Fazel Shabanpoor, Toshifumi Yokota, Shin'ichi Takeda, Yoshitsugu Aoki
Exon skipping using phosphorodiamidate morpholino oligomers (PMOs) is a promising treatment strategy for Duchenne muscular dystrophy (DMD). The most significant limitation of these clinically used compounds is their lack of delivery systems that target muscles; thus, cell-penetrating peptides are being developed to enhance uptake into muscles. Recently, we reported that uptake of peptide-conjugated PMOs into myofibers was mediated by scavenger receptor class A (SR-A), which binds negatively charged ligands...
January 25, 2019: Molecular Therapy. Nucleic Acids
Joseph L Jilek, Qian-Yu Zhang, Mei-Juan Tu, Pui Yan Ho, Zhijian Duan, Jing-Xin Qiu, Ai-Ming Yu
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths, warranting better therapies. Restoration of tumor-suppressive microRNAs depleted in hepatocellular carcinoma represents a new therapeutic strategy. Herein, we sought to identify a potent microRNA (miRNA) agent that could alleviate HCC tumor burden and improve survival. Among a collection of bioengineered noncoding RNA molecules produced through bacterial fermentation, we identified let-7c agent as the most potent inhibitor of HCC cell viability...
January 24, 2019: Molecular Therapy. Nucleic Acids
Jing Chen, Xiaobei Liu, Yichen Xu, Kai Zhang, Jiayuan Huang, Banzhou Pan, Dongqin Chen, Shiyun Cui, Haizhu Song, Rui Wang, Xiaoyuan Chu, Xiaoli Zhu, Longbang Chen
Chemoresistance remains a great obstacle in effective lung adenocarcinoma (LUAD) treatment. Previously, we verified the role of microRNA-200b (miR-200b) in the formation of docetaxel (DTX)-resistant LUAD cells. This study aims to investigate the mechanism underlying the low level of miR-200b in DTX-resistant LUAD cells. The real-time reverse transcription (RT2 ) lncRNA PCR array system was applied to explore lncRNAs that potentially regulated miR-200b in DTX-resistant LUAD cells. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contributed to the low miR-200b level in DTX-resistant LUAD cells...
January 18, 2019: Molecular Therapy. Nucleic Acids
Ji Hyun Kim, Chang Ho Lee, Seong-Wook Lee
The mechanism by which hepatitis C virus (HCV) causes fibrosis and other chronic liver diseases remains poorly understood. Previously, we observed that HCV infection induces microRNA-192 (miR-192) expression, which in turn upregulates transforming growth factor β1 (TGF-β1) in hepatocytes. In this study, we aimed to determine the roles and mechanisms of HCV-induced miR-192 expression during chronic liver injury and fibrosis and to identify potential target of the liver disease. Noticeably, miR-192 is secreted and transmitted through exosomes from HCV-replicating hepatocytes into hepatic stellate cells (HSCs)...
January 18, 2019: Molecular Therapy. Nucleic Acids
Di Wang, Jian Zheng, Xiaobai Liu, Yixue Xue, Libo Liu, Jun Ma, Qianru He, Zhen Li, Heng Cai, Yunhui Liu
The anti-angiogenic treatment of malignant glioma cells is an effective method to treat high-grade gliomas. However, due to the presence of vasculogenic mimicry (VM), the anti-angiogenic treatment of gliomas is not significantly effective in improving overall patient median survival. Therefore, this study investigated the mechanism of mimic formation of angiogenesis in gliomas. The results of this experiment indicate that the expression of upstream transcription factor 1 (USF1) is upregulated in glioma tissues and cells...
January 15, 2019: Molecular Therapy. Nucleic Acids
Yun Zou, Wenzhi Li, Juan Zhou, Jin Zhang, Yiran Huang, Zhong Wang
The clinical efficiency of everolimus, an mammalian target of rapamycin (mTOR) inhibitor, is palliative as sequential or second-line therapy for renal cell carcinoma (RCC). However, the limited response of everolimus in RCC remains uncertain. In the present study, everolimus-resistant RCC models were established to understand the mechanisms and to seek combination approaches. Consequently, the activation of ERK was found to contribute toward everolimus-acquired resistance and poor prognosis in patients with RCC...
January 10, 2019: Molecular Therapy. Nucleic Acids
Naseer Ahmad, Priyanka Kushwaha, Anirudha Karvande, Ashish Kumar Tripathi, Priyanka Kothari, Sulekha Adhikary, Vikram Khedgikar, Vijay Kumar Mishra, Ritu Trivedi
Post-menopausal condition augments the biological aging process, characterized by multiple metabolic disorders in which bone loss is the most prevalent outcome and usually coupled with sarcopenia. Coexistence of such associated pathogenesis have much worse health outcomes, compared to individuals with osteoporosis only. Pre- and post-natal bone development demands calcium from mother to fetus during pregnancy and lactation leading to a significant maternal skeletal loss. It follows an anabolic phase around weaning during which there is a notable recovery of the maternal skeleton...
January 10, 2019: Molecular Therapy. Nucleic Acids
Lianzhong Zhao, Xiaohan Zhang, Zhu Wu, Kun Huang, Xiaomei Sun, Huanchun Chen, Meilin Jin
The influenza A virus poses serious public health challenges worldwide. Strikingly, small noncoding microRNAs (miRNAs) that modulate gene expression are closely involved in antiviral responses, although the underlying mechanisms are essentially unknown. We now report that microRNA-340 (miR340) is downregulated following influenza A and other RNA virus infections, implying that host cells deplete miR340 as an antiviral defense mechanism. Accordingly, the inhibition or knockdown of endogenous miR340 clearly prevents the infection of cultured cells, whereas the forced expression of miR340 significantly enhances virus replication...
January 10, 2019: Molecular Therapy. Nucleic Acids
Sunhye Shin, Jung-Won Choi, Hanbyeol Moon, Chang Youn Lee, Jun-Hee Park, Jiyun Lee, Hyang-Hee Seo, Gyoonhee Han, Soyeon Lim, Seahyoung Lee, Sang Woo Kim, Ki-Chul Hwang
Recent studies have shown that several upstream signaling elements of apoptosis and necroptosis are closely associated with acute injury in the heart. In our study, we observed that miR-105 was notably dysregulated in rat hearts with myocardial infarction (MI). Thus, the purpose of this study was to test the hypothesis that miR-105 participates in the regulation of RIP3/p-MLKL- and BNIP3-dependent necroptosis/apoptosis in H9c2 cells and MI rat hearts. Our results show that the RIP3/p-MLKL necroptotic pathway and BNIP3-dependent apoptosis signaling are enhanced in H9c2 cells under hypoxic conditions, whereas, compared with these pathways in the controls, those in miR-105-treated H9c2 cells are suppressed...
January 10, 2019: Molecular Therapy. Nucleic Acids
Feng Zhao, Hongxin Lang, Zhe Wang, Tao Zhang, Dianbao Zhang, Rui Wang, Xuewen Lin, Xiaoyu Liu, Ping Shi, Xining Pang
Early in gestation, wounds in fetal skin heal by regeneration, in which microRNAs play key roles. Seq-915_x4024 is a novel microRNA candidate confirmed by deep sequencing and mirTools 2.0. It is highly expressed in fetal keratinocytes during early gestation. Using an in vitro wound-healing assay, Transwell cell migration assay, and MTS proliferation assay, we demonstrated that keratinocytes overexpressing seq-915_x4024 exhibited higher proliferative activity and the ability to promote fibroblast migration and fibroblast proliferation...
January 10, 2019: Molecular Therapy. Nucleic Acids
Eun Sook Kim, Jae Yeon Choi, Su Jin Hwang, In Hwa Bae
Although radiotherapy has been successfully applied to treat many cancer types, surviving cancer cells often acquire therapeutic resistance, leading to increased risk of local recurrence and distant metastases via modification of the tumor microenvironment. Previously, we reported that high expression of Bcl-w in cancer patients is significantly correlated with poor survival as well as malignant activity. However, the relationship between ionizing radiation (IR)-induced resistance and Bcl-w expression in cancer cells is currently unclear...
December 31, 2018: Molecular Therapy. Nucleic Acids
Yan Ma, Yizheng Wu, Junxin Chen, Kangmao Huang, Bin Ji, Zhijun Chen, Qiang Wang, Jianjun Ma, Shuying Shen, Jianfeng Zhang
Osteoarthritis (OA) is a common joint disease characterized by degradation of the articular cartilage and joint inflammation. Studies have revealed the importance of microRNAs in the regulation of chondrocyte apoptosis. MicroRNA deep sequencing of control and osteoarthritic cartilage has revealed that miR-10a-5p is significantly upregulated in osteoarthritic tissues. However, its role in these tissues remains unknown. The present study was conducted to investigate the effect of miR-10a-5p in promoting OA...
December 25, 2018: Molecular Therapy. Nucleic Acids
Monika Rech, Annika R Kuhn, Joost Lumens, Paolo Carai, Rick van Leeuwen, Wouter Verhesen, Robin Verjans, Julie Lecomte, Yilin Liu, Joost J F P Luiken, Ronny Mohren, Berta Cillero-Pastor, Stephane Heymans, Kèvin Knoops, Marc van Bilsen, Blanche Schroen
MicroRNA-103/107 regulate systemic glucose metabolism and insulin sensitivity. For this reason, inhibitory strategies for these microRNAs are currently being tested in clinical trials. Given the high metabolic demands of the heart and the abundant cardiac expression of miR-103/107, we questioned whether antagomiR-mediated inhibition of miR-103/107 in C57BL/6J mice impacts on cardiac function. Notably, fractional shortening decreased after 6 weeks of antagomiR-103 and -107 treatment. This was paralleled by a prolonged systolic radial and circumferential time to peak and by a decreased global strain rate...
December 22, 2018: Molecular Therapy. Nucleic Acids
Shijian Lv, Na Wang, Hong Lv, Jieqiong Yang, Jianwei Liu, Wei-Ping Li, Cong Zhang, Zi-Jiang Chen
Recurrent miscarriage (RM) is currently defined as two or more losses of a clinically established intrauterine pregnancy. Despite years of research, RM continues to be a clinically frustrating challenge for patients and physicians, and its etiology remains poorly understood. Accumulating evidence has suggested that epigenetic modifications are involved in early embryogenesis, and defects in epigenetic patterning contribute to the development of RM. Here, we studied the role of enhancer of zeste homolog 2 (EZH2) in the pathogenesis of RM and found that the EZH2 expression was significantly decreased in the villi from women with RM compared with that in control villi...
December 22, 2018: Molecular Therapy. Nucleic Acids
Kwon Daekee, Han Mi-Jung, Ji Minjun, Ahn Hee-Jin, Seo Kwang-Won, Kang Kyung-Sun
As the human lifespan has increased due to developments in medical technology, the number of patients with neurological diseases has rapidly increased. Therefore, studies on effective treatments for neurological diseases are becoming increasingly important. To perform these studies, it is essential to obtain a large number of patient-derived neural cells. The purpose of the present study was to establish a technology that allows the high-efficiency generation of genetically stable, direct-conversion-derived neural stem cells (dcNSCs) through the expression of a new combination of reprogramming factors, including a proto-oncogene...
December 20, 2018: Molecular Therapy. Nucleic Acids
Jian Gao, Thorsten Bergmann, Wenli Zhang, Maren Schiwon, Eric Ehrke-Schulz, Anja Ehrhardt
Gene therapy represents an attractive alternative to treat hemophilia B. Here we established three hepatocyte-derived cell lines based on Huh7, PLC/PRF/5, and Hep3B cells stably carrying a mutated canine FIX (cFIXmut) transgene containing a single point mutation in the catalytic domain. Based on these in vitro models resembling a commonly used canine large animal model, the tetracycline-controlled transcriptional activator (Tet-on)-inducible CRISPR/Cas9 system and an optimized donor were used to correct mutated cFIX gene through homology-directed repair (HDR)...
December 20, 2018: Molecular Therapy. Nucleic Acids
John Lockhart, John Canfield, Ezinne Francess Mong, Jeffrey VanWye, Hana Totary-Jain
mRNA therapeutics hold great promise for the treatment of human diseases. While incorporating naturally occurring modified nucleotides during synthesis has greatly increased their potency and safety, challenges in selective expression have hindered clinical applications. MicroRNA (miRNA)-regulated in vitro-transcribed mRNAs, called miRNA switches, have been used to control the expression of exogenous mRNA in a cell-selective manner. However, the effect of nucleotide modifications on miRNA-dependent silencing has not been examined...
December 18, 2018: Molecular Therapy. Nucleic Acids
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